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Binduga UE, Kopeć A, Skoczylas J, Szychowski KA. Comparison of the Cytotoxic Mechanisms of Different Garlic ( Allium sativum L.) Cultivars with the Crucial Involvement of Peroxisome Proliferator-Activated Receptor Gamma. Int J Mol Sci 2025; 26:387. [PMID: 39796240 PMCID: PMC11720107 DOI: 10.3390/ijms26010387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2024] [Revised: 01/01/2025] [Accepted: 01/02/2025] [Indexed: 01/13/2025] Open
Abstract
Garlic (Allium sativum L.) is one of the oldest known useful plants, valued for thousands of years. This plant contains many biologically active compounds, including polyphenols, sterols, cysteine-sulfoxides, carbohydrates, proteins, and amino acids. The aim of our study was to compare the antioxidant potential, cytotoxicity, and apoptosis induction properties of four garlic cultivars-Harnaś, Ornak, Violeta, and Morado-in human squamous carcinoma (SCC-15) cells, colon adenocarcinoma (CACO-2) cells, and normal fibroblasts (BJ). Additionally, we investigated the mRNA and protein expression of peroxisome proliferator-activated receptor gamma (PPARγ), microtubule-associated protein 1 light chain 3 (LC3A), superoxide dismutase 1 (SOD1), and catalase (CAT) after treatment with the studied garlic extracts. Our study demonstrated that high ROS production was correlated with the strong toxicity of the garlic extracts. All studied extracts produced a lesser increase in ROS in normal BJ fibroblasts and were less toxic to these cells. The expression patterns of PPARγ, LC3A, SOD1, and CAT, along with chromatographic analysis, suggest differing mechanisms among the garlic cultivars. The highest levels of catechin, a known PPARγ agonist, were detected in the Harnaś (3.892 µg/mL) and Ornak (3.189 µg/mL) cultivars. A high catechin content was correlated with similar changes in PPARγ and related SOD1 and LC3A. Our findings showed the health-promoting and anticancer properties of garlic. However, we could not definitively identify which polyphenol or how it is involved in PPARγ activation. Further studies are required to elucidate the role of PPARγ in the mechanism of action of garlic extracts.
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Affiliation(s)
- Urszula E. Binduga
- Department of Civilization Diseases and Regenerative Medicine, Medical College, University of Information Technology and Management in Rzeszów, St. Sucharskiego 2, 35-225 Rzeszów, Poland
| | - Aneta Kopeć
- Department of Human Nutrition and Dietetics, Faculty of Food Technology, Agricultural University of Krakow, St. Balicka 122, 30-149 Kraków, Poland; (A.K.); (J.S.)
| | - Joanna Skoczylas
- Department of Human Nutrition and Dietetics, Faculty of Food Technology, Agricultural University of Krakow, St. Balicka 122, 30-149 Kraków, Poland; (A.K.); (J.S.)
| | - Konrad A. Szychowski
- Department of Biotechnology and Cell Biology, Medical College, University of Information Technology and Management in Rzeszów, St. Sucharskiego 2, 35-225 Rzeszów, Poland;
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Saini A, Saini V, Deswal G, Chopra B, Grewal AS, Dhingra AK. Harnessing Therapeutic Potential of Allicin Against Cancer: An Exploratory Review. Anticancer Agents Med Chem 2025; 25:589-602. [PMID: 39851103 DOI: 10.2174/0118715206343978241223080625] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2024] [Revised: 11/04/2024] [Accepted: 11/05/2024] [Indexed: 01/26/2025]
Abstract
BACKGROUND The biological name of garlic is Allium sativum L., a familiar spice with various health benefits. These benefits are mainly attributable to the compound diversity of garlic, which includes saponins, polysaccharides, organic sulfides, and phenolic compounds. Allicin exhibits therapeutic activity such as antibacterial, anticancer, anti-inflammatory, immunomodulatory, anti-diabetic, and cardiovascular protection. This present study explores the anticancer potential of allicin, including cell line studies that examine its effects on various cancer types by analyzing the growth inhibition of cancer cells at different allicin concentrations. AIM This study aims to present a concise overview of allicin, update patent statistics, and provide detailed insights into its wide range of therapeutic benefits, with a particular emphasis on its anticancer properties. METHODS A literature review has been conducted using reliable sources, including ClinicalTrials.gov, ScienceDirect, PubMed, Scopus, and other reputable foundations, to assess the true potential of allicin in cancer therapeutics. RESULTS Allicin, a naturally occurring compound in garlic, represents a promising treatment approach for cancer due to its potent anticancer properties. Cell line studies have shown that various concentrations of allicin significantly inhibit cancer cell growth, underscoring its effectiveness against cancer types such as breast, pancreatic, liver, renal, osteosarcoma, gastric, colorectal, and stomach cancers. By effectively targeting cancer cells, allicin stands out as a potential therapeutic agent. CONCLUSION The primary goal of the review is to highlight the anticancer potential of allicin, along with an overview of clinical and patent studies.
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Affiliation(s)
- Anmol Saini
- Global Research Institute of Pharmacy, Radaur, Yamuna Nagar, Haryana, 135133, India
| | - Vishakha Saini
- Global Research Institute of Pharmacy, Radaur, Yamuna Nagar, Haryana, 135133, India
| | - Geeta Deswal
- Guru Gobind Singh College of Pharmacy, Yamuna Nagar, Haryana, 135001, India
| | - Bhawna Chopra
- Guru Gobind Singh College of Pharmacy, Yamuna Nagar, Haryana, 135001, India
| | - Ajmer Singh Grewal
- Guru Gobind Singh College of Pharmacy, Yamuna Nagar, Haryana, 135001, India
| | - Ashwani K Dhingra
- Global Research Institute of Pharmacy, Radaur, Yamuna Nagar, Haryana, 135133, India
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Bhuker S, Kaur A, Rajauria K, Tuli HS, Saini AK, Saini RV, Gupta M. Allicin: a promising modulator of apoptosis and survival signaling in cancer. Med Oncol 2024; 41:210. [PMID: 39060753 DOI: 10.1007/s12032-024-02459-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Accepted: 07/22/2024] [Indexed: 07/28/2024]
Abstract
According to the World Health Organization, cancer is the foremost cause of mortality globally. Various phytochemicals from natural sources have been extensively studied for their anticancer properties. Allicin, a powerful organosulfur compound derived from garlic, exhibits anticancer, antioxidant, anti-inflammatory, antifungal, and antibacterial properties. This review aims to update and evaluate the chemistry, composition, mechanisms of action, and pharmacokinetics Allicin. Allicin has garnered significant attention for its potential role in modulating Fas-FasL, Bcl2-Bax, PI3K-Akt-mTOR, autophagy, and miRNA pathways. At the molecular level, allicin induces the release of cytochrome c from the mitochondria and enhances the activation of caspases-3, -8, and -9. This is accompanied by the simultaneous upregulation of Bax and Fas expression in tumor cells. Allicin can inhibit excessive autophagy by activating the PI3K/Akt/mTOR and MAPK/ERK/mTOR signaling pathways. Allicin-loaded nano-formulations efficiently induce apoptosis in cancer cells while minimizing toxicity to normal cells. Safety and clinical aspects are meticulously scrutinized, providing insights into the tolerability and adverse effects associated with allicin administration, along with an overview of current clinical trials evaluating its therapeutic potential. In conclusion, this review underscores the promising prospects of allicin as a dietary-derived medicinal compound for cancer therapy. It emphasizes the need for further research to elucidate its precise mechanisms of action, optimize delivery strategies, and validate its efficacy in clinical settings.
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Affiliation(s)
- Sunaina Bhuker
- Department of Bio-Sciences & Technology, MMEC, Maharishi Markandeshwar (Deemed to Be University), Mullana, Haryana, 133207, India
| | - Avneet Kaur
- Department of Bio-Sciences & Technology, MMEC, Maharishi Markandeshwar (Deemed to Be University), Mullana, Haryana, 133207, India
| | - Kanitha Rajauria
- SRM Institute of Science and Technology, SRM Nagar, Kattankulathur, Tamil Nadu, 603203, India
| | - Hardeep Singh Tuli
- Department of Bio-Sciences & Technology, MMEC, Maharishi Markandeshwar (Deemed to Be University), Mullana, Haryana, 133207, India
| | - Adesh K Saini
- Department of Bio-Sciences & Technology, MMEC, Maharishi Markandeshwar (Deemed to Be University), Mullana, Haryana, 133207, India
- Central Research Laboratory, Maharishi Markandeshwar (Deemed to Be University), Mullana, Haryana, 133207, India
| | - Reena V Saini
- Department of Bio-Sciences & Technology, MMEC, Maharishi Markandeshwar (Deemed to Be University), Mullana, Haryana, 133207, India.
- Central Research Laboratory, Maharishi Markandeshwar (Deemed to Be University), Mullana, Haryana, 133207, India.
- Central Research Laboratory and Department of Bio-Sciences and Technology, MMEC, Maharishi Markandeshwar (Deemed to Be University), Mullana-Ambala, Haryana, 133207, India.
| | - Madhu Gupta
- Department of Pharmaceutics, Delhi Pharmaceutical Sciences and Research University, Pushp Vihar, New Delhi, 110017, India
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Jiang M, Wu W, Xiong Z, Yu X, Ye Z, Wu Z. Targeting autophagy drug discovery: Targets, indications and development trends. Eur J Med Chem 2024; 267:116117. [PMID: 38295689 DOI: 10.1016/j.ejmech.2023.116117] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Revised: 12/30/2023] [Accepted: 12/31/2023] [Indexed: 02/25/2024]
Abstract
Autophagy plays a vital role in sustaining cellular homeostasis and its alterations have been implicated in the etiology of many diseases. Drugs development targeting autophagy began decades ago and hundreds of agents were developed, some of which are licensed for the clinical usage. However, no existing intervention specifically aimed at modulating autophagy is available. The obstacles that prevent drug developments come from the complexity of the actual impact of autophagy regulators in disease scenarios. With the development and application of new technologies, several promising categories of compounds for autophagy-based therapy have emerged in recent years. In this paper, the autophagy-targeted drugs based on their targets at various hierarchical sites of the autophagic signaling network, e.g., the upstream and downstream of the autophagosome and the autophagic components with enzyme activities are reviewed and analyzed respectively, with special attention paid to those at preclinical or clinical trials. The drugs tailored to specific autophagy alone and combination with drugs/adjuvant therapies widely used in clinical for various diseases treatments are also emphasized. The emerging drug design and development targeting selective autophagy receptors (SARs) and their related proteins, which would be expected to arrest or reverse the progression of disease in various cancers, inflammation, neurodegeneration, and metabolic disorders, are critically reviewed. And the challenges and perspective in clinically developing autophagy-targeted drugs and possible combinations with other medicine are considered in the review.
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Affiliation(s)
- Mengjia Jiang
- Department of Pharmacology and Pharmacy, China Jiliang University, China
| | - Wayne Wu
- College of Osteopathic Medicine, New York Institute of Technology, USA
| | - Zijie Xiong
- Department of Pharmacology and Pharmacy, China Jiliang University, China
| | - Xiaoping Yu
- Department of Biology, China Jiliang University, China
| | - Zihong Ye
- Department of Biology, China Jiliang University, China
| | - Zhiping Wu
- Department of Pharmacology and Pharmacy, China Jiliang University, China.
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Li K, Uyanga VA, Wang X, Jiao H, Zhao J, Zhou Y, Li H, Lin H. Allicin Promotes Glucose Uptake by Activating AMPK through CSE/H 2S-Induced S-Sulfhydration in a Muscle-Fiber Dependent Way in Broiler Chickens. Mol Nutr Food Res 2024; 68:e2300622. [PMID: 38339885 DOI: 10.1002/mnfr.202300622] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Revised: 01/08/2024] [Indexed: 02/12/2024]
Abstract
SCOPE Allicin, a product of enzymatic reaction when garlic is injured, plays an important role in maintaining glucose homeostasis in mammals. However, the effect of allicin on glucose homeostasis in the state of insulin resistance remains to be elucidated. This study investigates the effect of allicin on glucose metabolism using different muscle fibers in a chicken model. METHODS AND RESULTS Day-old male Arbor Acres broilers are randomly divided into three groups and fed a basal diet supplemented with 0, 150, or 300 mg kg-1 allicin for 42 days. Results show that allicin improves the zootechnical performance of broilers at the finishing stage. The glucose loading test (2 g kg-1 body mass) indicates the regulatory role of allicin on glucose homeostasis. In vitro results demonstrate allicin increases glutathione (GSH) level and the expression of cystathionine γ lyase (CSE), leading to endogenous hydrogen sulfide (H2S) production in M. pectoralis major (PM) muscle-derived myotubes. Allicin stimulates adenosine monophosphate-activated protein kinase (AMPK) S-sulfhydration and AMPK phosphorylation to promote glucose uptake, which is suppressed in the presence of d,l-propargylglycine (PAG, a CSE inhibitor). CONCLUSION This study demonstrates that allicin induces AMPK S-sulfhydration and AMPK phosphorylation to promote glucose uptake via the CSE/H2S system in a muscle fiber-dependent manner.
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Affiliation(s)
- Kelin Li
- College of Animal Science and Technology, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Key Laboratory of Efficient Utilization of Non-grain Feed Resources (Co-construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, Shandong Agricultural University, Tai'an, 271000, China
| | - Victoria A Uyanga
- College of Animal Science and Technology, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Key Laboratory of Efficient Utilization of Non-grain Feed Resources (Co-construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, Shandong Agricultural University, Tai'an, 271000, China
| | - Xiaojuan Wang
- College of Animal Science and Technology, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Key Laboratory of Efficient Utilization of Non-grain Feed Resources (Co-construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, Shandong Agricultural University, Tai'an, 271000, China
| | - Hongchao Jiao
- College of Animal Science and Technology, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Key Laboratory of Efficient Utilization of Non-grain Feed Resources (Co-construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, Shandong Agricultural University, Tai'an, 271000, China
| | - Jingpeng Zhao
- College of Animal Science and Technology, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Key Laboratory of Efficient Utilization of Non-grain Feed Resources (Co-construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, Shandong Agricultural University, Tai'an, 271000, China
| | - Yunlei Zhou
- College of Chemistry and Material Science, Shandong Agricultural University, Tai'an, 271000, China
| | - Haifang Li
- College of Life Sciences, Shandong Agricultural University, Tai'an, 271000, China
| | - Hai Lin
- College of Animal Science and Technology, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Key Laboratory of Efficient Utilization of Non-grain Feed Resources (Co-construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, Shandong Agricultural University, Tai'an, 271000, China
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Govindasamy B, Muthu M, Gopal J, Chun S. A review on the impact of TRAIL on cancer signaling and targeting via phytochemicals for possible cancer therapy. Int J Biol Macromol 2023; 253:127162. [PMID: 37788732 DOI: 10.1016/j.ijbiomac.2023.127162] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Revised: 09/11/2023] [Accepted: 09/28/2023] [Indexed: 10/05/2023]
Abstract
Anticancer therapies have been the continual pursuit of this age. Cancer has been ravaging all across the globe breathing not just threats but demonstrating them. Remedies for cancer have been frantically sought after. Few have worked out, yet till date, the available cancer therapies have not delivered a holistic solution. In a world where the search for therapies is levitating towards natural remedies, solutions based on phytochemicals are highly prospective attractions. A lot has been achieved with inputs from plant resources, providing numerous natural remedies. In the current review, we intensely survey the progress achieved in the treatment of cancer through phytochemicals-based programmed cell death of cancer cells. More specifically, we have further reviewed and discussed the role of phytochemicals in activating apoptosis via Tumor Necrosis Factor-Alpha-Related Apoptosis-Inducing Ligand (TRAIL), which is a cell protein that can attach to certain molecules in cancer cells, killing cancer cells. The objective of this review is to enlist the various phytochemicals that are available for specifically contributing towards triggering the TRAIL cell protein-mediated cancer therapy and to point out the research gaps that require future research motivation. This is the first review of this kind in this research direction.
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Affiliation(s)
- Balasubramani Govindasamy
- Department of Product Development, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences (SIMATS), Thandalam, Chennai 602105, India
| | - Manikandan Muthu
- Department of Research and Innovation, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences (SIMATS), Thandalam, Chennai 602105, India
| | - Judy Gopal
- Department of Research and Innovation, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences (SIMATS), Thandalam, Chennai 602105, India
| | - Sechul Chun
- Department of Bioresources and Food Science, Institute of Natural Science and Agriculture, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul 05029, Republic of Korea.
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Yu H, Hao Z, Liu X, Wei Z, Tan R, Liu X, Chen Q, Chen Y, Zhou H, Liu Y, Fu Z. Autophagy blockage and lysosomal dysfunction are involved in diallyl sulfide-induced inhibition of malignant growth in hepatocellular carcinoma cells. ENVIRONMENTAL TOXICOLOGY 2023; 38:2100-2110. [PMID: 37209385 DOI: 10.1002/tox.23834] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/21/2023] [Revised: 04/23/2023] [Accepted: 05/01/2023] [Indexed: 05/22/2023]
Abstract
Diallyl sulfide (DAS), as a major component of garlic extracts, has been shown to inhibit growth of hepatocellular carcinoma cells (HCC), but the underlying mechanism is still elusive. In this study, we aimed to explore the involvement of autophagy in DAS-induced growth inhibition of HepG2 and Huh7 hepatocellular carcinoma cells. We studied growth of DAS-treated HepG2 and Huh7 cells using the MTS and clonogenic assays. Autophagic flux was examined by immunofluorescence and confocal microscopy. The expression levels of autophagy-related proteins AMPK, mTOR, p62, LC3-II, LAMP1, and cathepsin D in the HepG2 and Huh7 cells treated with DAS as well as the tumors formed by HepG2 cells in the nude mice in the presence or absence of DAS were examined using western blotting and immunohistochemistry analysis. We found that DAS treatment induced activation of AMPK/mTOR, and accumulation of LC3-II and p62 both in vivo and in vitro. DAS inhibited autophagic flux through blocking the fusion of autophagosomes with lysosomes. Furthermore, DAS induced an increase in lysosomal pH and inhibition of Cathepsin D maturation. Co-treatment with an autophagy inhibitor (Chloroquine, CQ) further enhanced the growth inhibitory activity of DAS in HCC cells. Thus, our findings indicate that autophagy is involved in DAS-mediated growth inhibition of HCC cells both in vitro and in vivo.
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Affiliation(s)
- Haiyan Yu
- Department of Pathology and Pathophysiology, School of Medicine, Jianghan University, Wuhan, People's Republic of China
| | - Zhiwei Hao
- Department of Pathology and Pathophysiology, School of Medicine, Jianghan University, Wuhan, People's Republic of China
| | - Xuemin Liu
- Department of Pathology and Pathophysiology, School of Medicine, Jianghan University, Wuhan, People's Republic of China
| | - Zhixuan Wei
- Department of Pathology and Pathophysiology, School of Medicine, Jianghan University, Wuhan, People's Republic of China
| | - Renming Tan
- Department of Pathology and Pathophysiology, School of Medicine, Jianghan University, Wuhan, People's Republic of China
| | - Xiaotian Liu
- Department of Pathology and Pathophysiology, School of Medicine, Jianghan University, Wuhan, People's Republic of China
| | - Qiongxia Chen
- Department of Pathology and Pathophysiology, School of Medicine, Jianghan University, Wuhan, People's Republic of China
| | - Ying Chen
- Department of Pathology and Pathophysiology, School of Medicine, Jianghan University, Wuhan, People's Republic of China
| | - Hongyan Zhou
- Department of Pathology and Pathophysiology, School of Medicine, Jianghan University, Wuhan, People's Republic of China
| | - Yuchen Liu
- Cancer Institute, School of Medicine, Jianghan University, Wuhan, People's Republic of China
| | - Zhengqi Fu
- Department of Pathology and Pathophysiology, School of Medicine, Jianghan University, Wuhan, People's Republic of China
- Cancer Institute, School of Medicine, Jianghan University, Wuhan, People's Republic of China
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Sun S, Liu X, Wei X, Zhang S, Wang W. Diallyl trisulfide induces pro-apoptotic autophagy via the AMPK/SIRT1 signalling pathway in human hepatocellular carcinoma HepG2 cell line. Food Nutr Res 2023; 66:8981. [PMID: 37868628 PMCID: PMC10588957 DOI: 10.29219/fnr.v66.8981] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Revised: 10/27/2022] [Accepted: 11/09/2022] [Indexed: 10/24/2023] Open
Abstract
Background Liver cancer is associated with a high mortality rate worldwide. Hepatocellular carcinoma (HCC) constitutes a large proportion of primary liver cancers, and most of its alterations currently remain untreatable. Diallyl trisulfide (DATS), the main chemical constituent of allicin, affects tumour development by regulating cell apoptosis. Allicin-induced autophagy could contribute to apoptosis in HepG2 cells. We rigorously examined the autophagy-related mechanism of allicin-induced apoptosis in HepG2 cells. We treated HepG2 cells with DATS to explore the effect of DATS on pro-apoptotic autophagy in HepG2 cell lines and examine its specific molecular mechanism. Methods HepG2 cells were treated with various concentrations of DATS for 24 and 48 h. Subsequently, cell viability was measured using the cell counting kit-8 (CCK-8) assay and cell clone formation assay. The HepG2 cell apoptosis was measured using Hoechst 33258 staining and western blotting. Autophagy and the AMP-activated protein kinase (AMPK)/NAD-dependent deacetylase sirtuin-1 (SIRT1) signalling pathway were detected using western blotting. Results Our results indicated that DATS inhibited HepG2 cell growth. Moreover, the ability of DATS to promote apoptosis in HepG2 cells increased with increasing concentration. We verified the phenomenon of DATS-induced autophagy in HepG2 cells and demonstrated that DATS treatment upregulated the protein expression of LC3-II/I. By measuring the expression of potential autophagy stimulators, we documented that DATS could induce pro-apoptotic autophagy by activating the AMPK/SIRT1 signalling pathway. Conclusion DATS induced pro-apoptotic autophagy via the AMPK/SIRT1 signalling pathway in the human HCC HepG2 cell line. Our findings further implicate allicin as a potential therapeutic agent against liver tumours in clinical settings, providing a basis for combining allicin with an autophagy agonist for treating liver cancer.
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Affiliation(s)
- Shuoshuo Sun
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Xiyu Liu
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Xiao Wei
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Shaohong Zhang
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
- The Affiliated Huaian NO. 1 People’s Hospital, Nanjing Medical University, Huaian, China
| | - Weimin Wang
- The Affiliated Huaian NO. 1 People’s Hospital, Nanjing Medical University, Huaian, China
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Du YX, Mamun AA, Lyu AP, Zhang HJ. Natural Compounds Targeting the Autophagy Pathway in the Treatment of Colorectal Cancer. Int J Mol Sci 2023; 24:7310. [PMID: 37108476 PMCID: PMC10138367 DOI: 10.3390/ijms24087310] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Revised: 04/03/2023] [Accepted: 04/12/2023] [Indexed: 04/29/2023] Open
Abstract
Autophagy is a highly conserved intracellular degradation pathway by which misfolded proteins or damaged organelles are delivered in a double-membrane vacuolar vesicle and finally degraded by lysosomes. The risk of colorectal cancer (CRC) is high, and there is growing evidence that autophagy plays a critical role in regulating the initiation and metastasis of CRC; however, whether autophagy promotes or suppresses tumor progression is still controversial. Many natural compounds have been reported to exert anticancer effects or enhance current clinical therapies by modulating autophagy. Here, we discuss recent advancements in the molecular mechanisms of autophagy in regulating CRC. We also highlight the research on natural compounds that are particularly promising autophagy modulators for CRC treatment with clinical evidence. Overall, this review illustrates the importance of autophagy in CRC and provides perspectives for these natural autophagy regulators as new therapeutic candidates for CRC drug development.
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Affiliation(s)
| | | | - Ai-Ping Lyu
- School of Chinese Medicine, Hong Kong Baptist University, 7 Baptist University Road, Kowloon Tong, Kowloon, Hong Kong SAR, China; (Y.-X.D.); (A.A.M.)
| | - Hong-Jie Zhang
- School of Chinese Medicine, Hong Kong Baptist University, 7 Baptist University Road, Kowloon Tong, Kowloon, Hong Kong SAR, China; (Y.-X.D.); (A.A.M.)
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10
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Health benefits of bioactive components in pungent spices mediated via the involvement of TRPV1 channel. Trends Food Sci Technol 2022. [DOI: 10.1016/j.tifs.2022.10.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
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Shiau JP, Chuang YT, Tang JY, Yang KH, Chang FR, Hou MF, Yen CY, Chang HW. The Impact of Oxidative Stress and AKT Pathway on Cancer Cell Functions and Its Application to Natural Products. Antioxidants (Basel) 2022; 11:1845. [PMID: 36139919 PMCID: PMC9495789 DOI: 10.3390/antiox11091845] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Revised: 09/14/2022] [Accepted: 09/16/2022] [Indexed: 01/10/2023] Open
Abstract
Oxidative stress and AKT serine-threonine kinase (AKT) are responsible for regulating several cell functions of cancer cells. Several natural products modulate both oxidative stress and AKT for anticancer effects. However, the impact of natural product-modulating oxidative stress and AKT on cell functions lacks systemic understanding. Notably, the contribution of regulating cell functions by AKT downstream effectors is not yet well integrated. This review explores the role of oxidative stress and AKT pathway (AKT/AKT effectors) on ten cell functions, including apoptosis, autophagy, endoplasmic reticulum stress, mitochondrial morphogenesis, ferroptosis, necroptosis, DNA damage response, senescence, migration, and cell-cycle progression. The impact of oxidative stress and AKT are connected to these cell functions through cell function mediators. Moreover, the AKT effectors related to cell functions are integrated. Based on this rationale, natural products with the modulating abilities for oxidative stress and AKT pathway exhibit the potential to regulate these cell functions, but some were rarely reported, particularly for AKT effectors. This review sheds light on understanding the roles of oxidative stress and AKT pathway in regulating cell functions, providing future directions for natural products in cancer treatment.
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Affiliation(s)
- Jun-Ping Shiau
- Division of Breast Oncology and Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan or
| | - Ya-Ting Chuang
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Jen-Yang Tang
- School of Post-Baccalaureate Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaoshiung Medical University, Kaohsiung 80708, Taiwan
| | - Kun-Han Yang
- Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Fang-Rong Chang
- Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Ming-Feng Hou
- Division of Breast Oncology and Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan or
- Department of Biomedical Science and Environmental Biology, College of Life Science, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Ching-Yu Yen
- Department of Oral and Maxillofacial Surgery, Chi-Mei Medical Center, Tainan 71004, Taiwan
- School of Dentistry, Taipei Medical University, Taipei 11031, Taiwan
| | - Hsueh-Wei Chang
- Department of Biomedical Science and Environmental Biology, College of Life Science, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Center for Cancer Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
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12
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Zhou Y, Li X, Luo W, Zhu J, Zhao J, Wang M, Sang L, Chang B, Wang B. Allicin in Digestive System Cancer: From Biological Effects to Clinical Treatment. Front Pharmacol 2022; 13:903259. [PMID: 35770084 PMCID: PMC9234177 DOI: 10.3389/fphar.2022.903259] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Accepted: 05/23/2022] [Indexed: 12/24/2022] Open
Abstract
Allicin is the main active ingredient in freshly-crushed garlic and some other allium plants, and its anticancer effect on cancers of digestive system has been confirmed in many studies. The aim of this review is to summarize epidemiological studies and in vitro and in vivo investigations on the anticancer effects of allicin and its secondary metabolites, as well as their biological functions. In epidemiological studies of esophageal cancer, liver cancer, pancreatic cancer, and biliary tract cancer, the anticancer effect of garlic has been confirmed consistently. However, the results obtained from epidemiological studies in gastric cancer and colon cancer are inconsistent. In vitro studies demonstrated that allicin and its secondary metabolites play an antitumor role by inhibiting tumor cell proliferation, inducing apoptosis, controlling tumor invasion and metastasis, decreasing angiogenesis, suppressing Helicobacter pylori, enhancing the efficacy of chemotherapeutic drugs, and reducing the damage caused by chemotherapeutic drugs. In vivo studies further demonstrate that allicin and its secondary metabolites inhibit cancers of the digestive system. This review describes the mechanisms against cancers of digestive system and therapeutic potential of allicin and its secondary metabolites.
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Affiliation(s)
- Yang Zhou
- Department of Gastroenterology, The First Affiliated Hospital of China Medical University, Shenyang, China
- The Second Clinical College, China Medical University, Shenyang, China
| | - Xingxuan Li
- The Second Clinical College, China Medical University, Shenyang, China
| | - Wenyu Luo
- The Second Clinical College, China Medical University, Shenyang, China
| | - Junfeng Zhu
- Department of Clinical Laboratory, Affiliated Hospital of Guilin Medical University, Guilin, China
| | - Jingwen Zhao
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Mengyao Wang
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Lixuan Sang
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Bing Chang
- Department of Gastroenterology, The First Affiliated Hospital of China Medical University, Shenyang, China
- *Correspondence: Bing Chang,
| | - Bingyuan Wang
- Department of Geriatric Medicine, The First Affiliated Hospital of China Medical University, Shenyang, China
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13
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Fan ZX, Zhang J, Wang X, Miao GY. Convergent Fabrication of Allicin Loaded Polymeric Nanoparticles for Treatment of In Vitro Squamous Carcinoma Cells and Systemic Toxicity. J CLUST SCI 2022. [DOI: 10.1007/s10876-022-02246-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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14
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Xu S, Liao Y, Wang Q, Liu L, Yang W. Current studies and potential future research directions on biological effects and related mechanisms of allicin. Crit Rev Food Sci Nutr 2022; 63:7722-7748. [PMID: 35293826 DOI: 10.1080/10408398.2022.2049691] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Allicin, a thiosulfonate extract from freshly minced garlic, has been reported to have various biological effects on different organs and systems of animals and human. It can reduce oxidative stress, inhibit inflammatory response, resist pathogen infection and regulate intestinal flora. In addition, dozens of studies also demonstrated allicin could reduce blood glucose level, protect cardiovascular system and nervous system, and fight against cancers. Allicin was widely used in disease prevention and health care. However, more investigations on human cohort study are needed to verify the biological or clinical effects of allicin in the future. In this review, we summarized the biological effects of allicin from previous outstanding and valuable studies and provided useful information for future studies on the health effects of allicin.
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Affiliation(s)
- Shiyin Xu
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Department of Nutrition and Food Hygiene and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- China-DRIs Expert Committee on Other Dietary Ingredients, Sun Yat-sen University, Guangzhou, China
| | - Yuxiao Liao
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Department of Nutrition and Food Hygiene and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- China-DRIs Expert Committee on Other Dietary Ingredients, Sun Yat-sen University, Guangzhou, China
| | - Qi Wang
- Department of Epidemiology and Biostatistics, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Liegang Liu
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Department of Nutrition and Food Hygiene and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- China-DRIs Expert Committee on Other Dietary Ingredients, Sun Yat-sen University, Guangzhou, China
| | - Wei Yang
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Department of Nutrition and Food Hygiene and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- China-DRIs Expert Committee on Other Dietary Ingredients, Sun Yat-sen University, Guangzhou, China
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15
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Dong C, Chen Z, Zhu L, Bsoul N, Wu H, Jiang J, Chen X, Lai Y, Yu G, Gu Y, Guo X, Gao W. Diallyl Trisulfide Enhances the Survival of Multiterritory Perforator Skin Flaps. Front Pharmacol 2022; 13:809034. [PMID: 35242032 PMCID: PMC8885991 DOI: 10.3389/fphar.2022.809034] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Accepted: 01/04/2022] [Indexed: 12/13/2022] Open
Abstract
The multiterritory perforator flap is one of the widest flap patterns used to repair tissue defects. However, flap necrosis of the distal part is still a challenging issue for plastic surgeons. Diallyl trisulfide (DATS) is an efficient ingredient extracted from garlic, exerting many important effects on different diseases. Our experiment aims to reveal whether DATS has a beneficial effect on the survival of perforator flaps and to explore its mechanism of action. The results showed that DATS enhanced angiogenesis and autophagy and reduced cell apoptosis and oxidative stress, thereby improving the survival rate of skin flaps. After co-administration with autophagy inhibitor 3-methyladenine (3MA), perforator flap survival was further improved. Mechanistically, we showed that PI3K/Akt and AMPK-HIF-1α signaling pathways in flap were activated under DATS treatment. All in all, DATS promoted the survival of multiterritory perforator flaps via the synergistic regulation of PI3K/Akt and AMPK-HIF-1α signaling pathways, and inhibition of DATS-induced autophagy further improves flap survival.
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Affiliation(s)
- Chengji Dong
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.,Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, China.,The Second Clinical Medical College of Wenzhou Medical University, Wenzhou, China
| | - Zhuliu Chen
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.,Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, China.,The Second Clinical Medical College of Wenzhou Medical University, Wenzhou, China
| | - Linxin Zhu
- Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, China.,The Second Clinical Medical College of Wenzhou Medical University, Wenzhou, China
| | - Najeeb Bsoul
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.,Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, China
| | - Hongqiang Wu
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.,Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, China.,The Second Clinical Medical College of Wenzhou Medical University, Wenzhou, China
| | - Jingtao Jiang
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.,Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, China.,The Second Clinical Medical College of Wenzhou Medical University, Wenzhou, China
| | - Xuankuai Chen
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.,Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, China.,The Second Clinical Medical College of Wenzhou Medical University, Wenzhou, China
| | - Yingying Lai
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.,Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, China.,The Second Clinical Medical College of Wenzhou Medical University, Wenzhou, China
| | - Gaoxiang Yu
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.,Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, China.,The Second Clinical Medical College of Wenzhou Medical University, Wenzhou, China
| | - Yanlan Gu
- Department of Histology and Embryology, Wenzhou Medical University, Zhejiang, China
| | - Xiaoshan Guo
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.,Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, China
| | - Weiyang Gao
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.,Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, China
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16
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Anticancer potential of allicin: A review. Pharmacol Res 2022; 177:106118. [DOI: 10.1016/j.phrs.2022.106118] [Citation(s) in RCA: 48] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 02/03/2022] [Accepted: 02/03/2022] [Indexed: 12/12/2022]
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17
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Rahman MA, Park MN, Rahman MDH, Rashid MM, Islam R, Uddin MJ, Hannan MA, Kim B. p53 Modulation of Autophagy Signaling in Cancer Therapies: Perspectives Mechanism and Therapeutic Targets. Front Cell Dev Biol 2022; 10:761080. [PMID: 35155422 PMCID: PMC8827382 DOI: 10.3389/fcell.2022.761080] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Accepted: 01/04/2022] [Indexed: 12/22/2022] Open
Abstract
The key tumor suppressor protein p53, additionally known as p53, represents an attractive target for the development and management of anti-cancer therapies. p53 has been implicated as a tumor suppressor protein that has multiple aspects of biological function comprising energy metabolism, cell cycle arrest, apoptosis, growth and differentiation, senescence, oxidative stress, angiogenesis, and cancer biology. Autophagy, a cellular self-defense system, is an evolutionarily conserved catabolic process involved in various physiological processes that maintain cellular homeostasis. Numerous studies have found that p53 modulates autophagy, although the relationship between p53 and autophagy is relatively complex and not well understood. Recently, several experimental studies have been reported that p53 can act both an inhibitor and an activator of autophagy which depend on its cellular localization as well as its mode of action. Emerging evidences have been suggested that the dual role of p53 which suppresses and stimulates autophagy in various cencer cells. It has been found that p53 suppression and activation are important to modulate autophagy for tumor promotion and cancer treatment. On the other hand, activation of autophagy by p53 has been recommended as a protective function of p53. Therefore, elucidation of the new functions of p53 and autophagy could contribute to the development of novel therapeutic approaches in cancer biology. However, the underlying molecular mechanisms of p53 and autophagy shows reciprocal functional interaction that is a major importance for cancer treatment and manegement. Additionally, several synthetic drugs and phytochemicals have been targeted to modulate p53 signaling via regulation of autophagy pathway in cancer cells. This review emphasizes the current perspectives and the role of p53 as the main regulator of autophagy-mediated novel therapeutic approaches against cancer treatment and managements.
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Affiliation(s)
- Md Ataur Rahman
- Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul, South Korea
- Korean Medicine-Based Drug Repositioning Cancer Research Center, College of Korean Medicine, Kyung Hee University, Seoul, South Korea
- Global Biotechnology & Biomedical Research Network (GBBRN), Department of Biotechnology and Genetic Engineering, Faculty of Biological Sciences, Islamic University, Kushtia, Bangladesh
- *Correspondence: Md Ataur Rahman, ; Bonglee Kim,
| | - Moon Nyeo Park
- Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul, South Korea
- Korean Medicine-Based Drug Repositioning Cancer Research Center, College of Korean Medicine, Kyung Hee University, Seoul, South Korea
| | - MD Hasanur Rahman
- Department of Biotechnology and Genetic Engineering, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj, Bangladesh
- ABEx Bio-Research Center, Dhaka, Bangladesh
| | - Md Mamunur Rashid
- Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, United States
| | - Rokibul Islam
- Department of Biotechnology and Genetic Engineering, Faculty of Biological Sciences, Islamic University, Kushtia, Bangladesh
- Department of Biochemistry, College of Medicine, Hallym University, Chuncheon, South Korea
| | - Md Jamal Uddin
- ABEx Bio-Research Center, Dhaka, Bangladesh
- Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul, Korea
| | - Md Abdul Hannan
- Department of Biochemistry and Molecular Biology, Bangladesh Agricultural University, Mymensingh, Bangladesh
| | - Bonglee Kim
- Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul, South Korea
- Korean Medicine-Based Drug Repositioning Cancer Research Center, College of Korean Medicine, Kyung Hee University, Seoul, South Korea
- *Correspondence: Md Ataur Rahman, ; Bonglee Kim,
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18
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Rauf A, Abu-Izneid T, Thiruvengadam M, Imran M, Olatunde A, Shariati MA, Bawazeer S, Naz S, Shirooie S, Sanches-Silva A, Farooq U, Kazhybayeva G. Garlic (Allium sativum L.): Its Chemistry, Nutritional Composition, Toxicity, and Anticancer Properties. Curr Top Med Chem 2022; 22:957-972. [PMID: 34749610 DOI: 10.2174/1568026621666211105094939] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Revised: 09/04/2021] [Accepted: 09/14/2021] [Indexed: 11/22/2022]
Abstract
The current review discuss the chemistry, nutritional composition, toxicity, and biological functions of garlic and its bioactive compounds against various types of cancers via different anticancer mechanisms. Several scientific documents were found in reliable literature and searched in databases viz Science Direct, PubMed, Web of Science, Scopus, and Research Gate were carried out using keywords such as "garlic", "garlic bioactive compounds", "anticancer mechanisms of garlic", "nutritional composition of garlic", and others. Garlic contains several phytoconstituents with activities against cancer, and compounds such as diallyl trisulfide (DATS), allicin, and diallyl disulfide (DADS), diallyl sulfide (DAS), and allyl mercaptan (AM). The influence of numerous garlic- derived products, phytochemicals, and nanoformulations on the liver, oral, prostate, breast, gastric, colorectal, skin, and pancreatic cancers has been studied. Based on our search, the bioactive molecules in garlic were found to inhibit the various phases of cancer. Moreover, the compounds in this plant also abrogate the peroxidation of lipids, activity of nitric oxide synthase, epidermal growth factor (EGF) receptor, nuclear factor-kappa B (NF-κB), protein kinase C, and regulate cell cycle and survival signaling cascades. Hence, garlic and its bioactive molecules exhibit the aforementioned mechanistic actions, and thus, they could be used to inhibit the induction, development, and progression of cancer. The review describes the nutritional composition of garlic, its bioactive molecules, and nanoformulations against various types of cancers, as well as the potential for developing these agents as antitumor drugs.
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Affiliation(s)
- Abdur Rauf
- Department of Chemistry, University of Swabi, Swabi, Anbar, 23430, KPK, Pakistan
| | - Tareq Abu-Izneid
- Pharmaceutical Sciences, College of Pharmacy, Al Ain University, Al Ain Campus, United Arab Emirates
| | - Muthu Thiruvengadam
- Department of Crop Science, College of Sanghuh Life Science, Konkuk University, Seoul, 05029, South Korea
| | - Muhammad Imran
- University Institute of Diet & Nutritional Sciences, Faculty of Allied Health Sciences, The University of Lahore, Punjab, Pakistan
| | - Ahmed Olatunde
- Department of Biochemistry, Abubakar Tafawa Balewa University, Bauchi, 740272, Nigeria
| | - Mohammad Ali Shariati
- K.G. Razumovsky Moscow State University of Technologies and Management [the First Cossack University], Moscow, Russian Federation
| | - Saud Bawazeer
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Saima Naz
- Department of Biotechnology, Bacha Khan University, Charsadda, KPK, Pakistan
| | - Samira Shirooie
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Ana Sanches-Silva
- National Institute for Agricultural and Veterinary Research, 4485-655, Vila do Conde, Portugal
- Center for Study in Animal Science (CECA), ICETA, University of Oporto, Oporto, Portugal
| | - Umar Farooq
- Department of Chemistry, COMSATS University Islamabad, Abbottabad-campus, Pakistan
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19
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Wang Y, Ge F, Sharma A, Rudan O, Setiawan MF, Gonzalez-Carmona MA, Kornek MT, Strassburg CP, Schmid M, Schmidt-Wolf IGH. Immunoautophagy-Related Long Noncoding RNA (IAR-lncRNA) Signature Predicts Survival in Hepatocellular Carcinoma. BIOLOGY 2021; 10:1301. [PMID: 34943216 PMCID: PMC8698564 DOI: 10.3390/biology10121301] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Revised: 11/29/2021] [Accepted: 12/07/2021] [Indexed: 12/27/2022]
Abstract
BACKGROUND The dysregulation of autophagy and immunological processes has been linked to various pathophysiological conditions, including cancer. Most notably, their particular involvement in hepatocellular carcinoma (HCC) is becoming increasingly evident. This has led to the possibility of developing a prognostic signature based on immuno-autophagy-related (IAR) genes. Given that long non-coding RNAs (lncRNAs) also play a special role in HCC, a combined signature utilizing IAR genes and HCC-associated long noncoding RNAs (as IARlncRNA) may potentially help in the clinical scenario. METHOD We used Pearson correlation analysis, Kaplan-Meier survival curves, univariate and multivariate Cox regression, and ROC curves to generate and validate a prognostic immuno-autophagy-related long non-coding RNA (IARlncRNA) signature. The Chi-squared test was utilized to investigate the correlation between the obtained signature and the clinical characteristics. CIBERSORT algorithms and the Wilcoxon rank sum test were applied to investigate the correlation between signature and infiltrating immune cells. GO and KEGG analyses were performed to derived signature-dependent pathways. RESULTS Herein, we build an IAR-lncRNA signature (as first in the literature) and demonstrate its prognostic ability in hepatocellular carcinoma. Primarily, we identified three IARlncRNAs (MIR210HG, AC099850.3 and CYTOR) as unfavorable prognostic determinants. The obtained signature predicted the high-risk HCC group with shorter overall survival, and was further associated with clinical characteristics such as tumor grade (t = 10.918, p = 0.001). Additionally, several infiltrating immune cells showed varied fractions between the low-risk group and the high-risk HCC groups in association with the obtained signature. In addition, pathways analysis described by the signature clearly distinguishes both risk groups in HCC. CONCLUSIONS The immuno-autophagy-related long non-coding RNA (IARlncRNA) signature we established exhibits a prognostic ability in hepatocellular carcinoma. To our knowledge, this is the first attempt in the literature to combine three determinants (immune, autophagy and LnRNAs), thus requiring molecular validation of this obtained signature in clinical samples.
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Affiliation(s)
- Yulu Wang
- Center for Integrated Oncology (CIO), Department of Integrated Oncology, University Hospital of Bonn, 53127 Bonn, Germany; (Y.W.); (F.G.); (A.S.); (O.R.); (M.F.S.)
| | - Fangfang Ge
- Center for Integrated Oncology (CIO), Department of Integrated Oncology, University Hospital of Bonn, 53127 Bonn, Germany; (Y.W.); (F.G.); (A.S.); (O.R.); (M.F.S.)
| | - Amit Sharma
- Center for Integrated Oncology (CIO), Department of Integrated Oncology, University Hospital of Bonn, 53127 Bonn, Germany; (Y.W.); (F.G.); (A.S.); (O.R.); (M.F.S.)
- Department of Neurosurgery, University Hospital of Bonn, 53127 Bonn, Germany
| | - Oliver Rudan
- Center for Integrated Oncology (CIO), Department of Integrated Oncology, University Hospital of Bonn, 53127 Bonn, Germany; (Y.W.); (F.G.); (A.S.); (O.R.); (M.F.S.)
| | - Maria F. Setiawan
- Center for Integrated Oncology (CIO), Department of Integrated Oncology, University Hospital of Bonn, 53127 Bonn, Germany; (Y.W.); (F.G.); (A.S.); (O.R.); (M.F.S.)
| | - Maria A. Gonzalez-Carmona
- Department of Internal Medicine I, University Hospital of Bonn, 53127 Bonn, Germany; (M.A.G.-C.); (M.T.K.); (C.P.S.)
| | - Miroslaw T. Kornek
- Department of Internal Medicine I, University Hospital of Bonn, 53127 Bonn, Germany; (M.A.G.-C.); (M.T.K.); (C.P.S.)
| | - Christian P. Strassburg
- Department of Internal Medicine I, University Hospital of Bonn, 53127 Bonn, Germany; (M.A.G.-C.); (M.T.K.); (C.P.S.)
| | - Matthias Schmid
- Institute of Medical Biometry, Informatics and Epidemiology, University Hospital of Bonn, 53127 Bonn, Germany;
| | - Ingo G. H. Schmidt-Wolf
- Center for Integrated Oncology (CIO), Department of Integrated Oncology, University Hospital of Bonn, 53127 Bonn, Germany; (Y.W.); (F.G.); (A.S.); (O.R.); (M.F.S.)
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20
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Targeting Drug Chemo-Resistance in Cancer Using Natural Products. Biomedicines 2021; 9:biomedicines9101353. [PMID: 34680470 PMCID: PMC8533186 DOI: 10.3390/biomedicines9101353] [Citation(s) in RCA: 73] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2021] [Revised: 09/22/2021] [Accepted: 09/23/2021] [Indexed: 02/07/2023] Open
Abstract
Cancer is one of the leading causes of death globally. The development of drug resistance is the main contributor to cancer-related mortality. Cancer cells exploit multiple mechanisms to reduce the therapeutic effects of anticancer drugs, thereby causing chemotherapy failure. Natural products are accessible, inexpensive, and less toxic sources of chemotherapeutic agents. Additionally, they have multiple mechanisms of action to inhibit various targets involved in the development of drug resistance. In this review, we have summarized the basic research and clinical applications of natural products as possible inhibitors for drug resistance in cancer. The molecular targets and the mechanisms of action of each natural product are also explained. Diverse drug resistance biomarkers were sensitive to natural products. P-glycoprotein and breast cancer resistance protein can be targeted by a large number of natural products. On the other hand, protein kinase C and topoisomerases were less sensitive to most of the studied natural products. The studies discussed in this review will provide a solid ground for scientists to explore the possible use of natural products in combination anticancer therapies to overcome drug resistance by targeting multiple drug resistance mechanisms.
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21
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Jafarzadeh A, Marzban H, Nemati M, Jafarzadeh S, Mahjoubin-Tehran M, Hamblin MR, Mirzaei H, Mirzaei HR. Dysregulated expression of miRNAs in immune thrombocytopenia. Epigenomics 2021; 13:1315-1325. [PMID: 34498489 DOI: 10.2217/epi-2021-0092] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
In recent years the critical role of miRNAs has been established in many diseases, including autoimmune disorders. Immune thrombocytopenia purpura (ITP) is a predominant autoimmune disease, in which aberrant expression of miRNAs has been observed, suggesting that miRNAs are involved in its development. miRNAs could induce an imbalance in the T helper (Th)1/Th2 cell and Th17/Treg cell-related responses. Moreover, they could also cause alterations in Th9 and Th22 cell responses, and activate Tfh (T follicular helper) cell-dependent auto-reactive B cells, thus influencing megakaryogenesis. Herein, we summarize the role of immune-related miRNAs in ITP pathogenesis, and look forward to clinical applications.
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Affiliation(s)
- Abdollah Jafarzadeh
- Department of Immunology, School of Medicine, Kerman University of Medical Sciences, 76169-13555, Kerman, Iran.,Department of Immunology, School of Medicine, Rafsanjan University of Medical Sciences, 7718175911, Rafsanjan, Iran
| | - Havva Marzban
- Department of Pathology & Experimental Animals, Razi Vaccine & Serum Research Institute, Agricultural Research, Education & Extension Organization (AREEO), 31975/148 Karaj, Iran
| | - Maryam Nemati
- Immunology of Infectious Diseases Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, 77181/75911, Rafsanjan, Iran.,Department of Hematology & Laboratory Sciences, School of Para-Medicine, Kerman University of Medical Sciences, 76169-13555, Kerman, Iran
| | - Sara Jafarzadeh
- Student Research Committee, School of Medicine, Kerman University of Medical Sciences, 76169-13555, Kerman, Iran
| | - Maryam Mahjoubin-Tehran
- Department of Medical Biotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, 13131- 99137, Mashhad, Iran
| | - Michael R Hamblin
- Laser Research Centre, Faculty of Health Science, University of Johannesburg, 2028 Doornfontein, South Africa
| | - Hamed Mirzaei
- Research Center for Biochemistry & Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, 87159-88141, Kashan, Iran.,Student Research Committee, Kashan University of Medical Sciences, 87159-88141, Kashan, Iran
| | - Hamid Reza Mirzaei
- Department of Medical Immunology, School of Medicine, Tehran University of Medical Sciences, 1417613151, Tehran, Iran
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22
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Li Y, Gao S, Du X, Ji J, Xi Y, Zhai G. Advances in autophagy as a target in the treatment of tumours. J Drug Target 2021; 30:166-187. [PMID: 34319838 DOI: 10.1080/1061186x.2021.1961792] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Autophagy is a multi-step lysosomal degradation process, which regulates energy and material metabolism and has been used to maintain homeostasis. Autophagy has been shown to be involved in the regulation of health and disease. But at present, there is no consensus on the relationship between autophagy and tumour, and we consider that it plays a dual role in the occurrence and development of tumour. That is to say, under certain conditions, it can inhibit the occurrence of tumour, but it can also promote the process of tumour. Therefore, autophagy could be used as a target for tumour treatment. The regulation of autophagy plays a synergistic role in the radiotherapy, chemotherapy, phototherapy and immunotherapy of tumour, and nano drug delivery system provides a promising strategy for improving the efficacy of autophagy regulation. This review summarised the progress in the regulatory pathways and factors of autophagy as well as nanoformulations as carriers for the delivery of autophagy modulators.
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Affiliation(s)
- Yingying Li
- Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, PR China
| | - Shan Gao
- Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, PR China
| | - Xiyou Du
- Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, PR China
| | - Jianbo Ji
- Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, PR China
| | - Yanwei Xi
- Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, PR China
| | - Guangxi Zhai
- Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, PR China
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Guo H, Fan Q. Identification of the HMMR Gene as a Diagnostic and Prognostic Biomarker in Hepatocellular Carcinoma Based on Integrated Bioinformatics Analysis. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2021; 2021:5970085. [PMID: 34221079 PMCID: PMC8221880 DOI: 10.1155/2021/5970085] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Revised: 06/02/2021] [Accepted: 06/08/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND We aimed to investigate the expression of the hyaluronan-mediated motility receptor (HMMR) gene in hepatocellular carcinoma (HCC) and nonneoplastic tissues and to investigate the diagnostic and prognostic value of HMMR. METHOD With the reuse of the publicly available The Cancer Genome Atlas (TCGA) data, 374 HCC patients and 50 nonneoplastic tissues were used to investigate the diagnostic and prognostic values of HMMR genes by receiver operating characteristic (ROC) curve analysis and survival analysis. All patients were divided into low- and high-expression groups based on the median value of HMMR expression level. Univariate and multivariate Cox regression analysis were used to identify prognostic factors. Gene set enrichment analysis (GSEA) was performed to explore the potential mechanism of the HMMR genes involved in HCC. The diagnostic and prognostic values were further validated in an external cohort from the International Cancer Genome Consortium (ICGC). RESULTS HMMR mRNA expression was significantly elevated in HCC tissues compared with that in normal tissues from both TCGA and the ICGC cohorts (all P values <0.001). Increased HMMR expression was significantly associated with histologic grade, pathological stage, and survival status (all P values <0.05). The area under the ROC curve for HMMR expression in HCC and normal tissues was 0.969 (95% CI: 0.948-0.983) in the TCGA cohort and 0.956 (95% CI: 0.932-0.973) in the ICGC cohort. Patients with high HMMR expression had a poor prognosis than patients with low expression group in both cohorts (all P < 0.001). Univariate and multivariate analysis also showed that HMMR is an independent predictor factor associated with overall survival in both cohorts (all P values <0.001). GSEA showed that genes upregulated in the high-HMMR HCC subgroup were mainly significantly enriched in the cell cycle pathway, pathways in cancer, and P53 signaling pathway. CONCLUSION HMMR is expressed at high levels in HCC. HMMR overexpression may be an unfavorable prognostic factor for HCC.
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Affiliation(s)
- Honglan Guo
- Department of Gastroenterology, The First People's Hospital of Chenzhou City, Chenzhou 423000, Hunan, China
| | - Qinqiao Fan
- Department of Hepatobiliary, The First People's Hospital of Chenzhou City, Chenzhou 423000, Hunan, China
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Li J, Dadmohammadi Y, Abbaspourrad A. Flavor components, precursors, formation mechanisms, production and characterization methods: garlic, onion, and chili pepper flavors. Crit Rev Food Sci Nutr 2021; 62:8265-8287. [PMID: 34028311 DOI: 10.1080/10408398.2021.1926906] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/30/2022]
Abstract
There is an enormous demand in the food industry to shift toward natural flavors. However, most flavor molecules are significantly unstable outside their original sources. Moreover, limited studies are focused on the flavor formation mechanisms, regeneration methods, and stability, which could help facilitate this replacement by establishing a link between food processing conditions and flavor generation.This scoping review summarizes major findings related to the identification of garlic, onion, and chili pepper flavors and their precursor molecules, formation mechanisms, generation of flavors and precursors, characterization methods, and precursor stability under thermal food processing conditions. The findings confirmed that the allium flavors could be generated by alliin and isoalliin precursors through thermal processing. Also, the literature lacks detailed knowledge about chili pepper flavor's precursors, and only capsaicinoids have been reported as a thermally stable chili pepper flavor.Although numerous studies have focused on this area, there is still a lack of detailed applicable knowledge. Future investigations can be framed into (1) Development of efficient methods to generate flavors during food processing; (2) Improvement of flavors' stability; (3) Understanding the interactions of flavors and their precursors with other food ingredients and additives; and (4) Characterization of the organoleptic properties of flavors.
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Affiliation(s)
- Jieying Li
- Department of Food Science, College of Agriculture and Life Sciences, Cornell University, Ithaca, New York, USA
| | - Younas Dadmohammadi
- Department of Food Science, College of Agriculture and Life Sciences, Cornell University, Ithaca, New York, USA
| | - Alireza Abbaspourrad
- Department of Food Science, College of Agriculture and Life Sciences, Cornell University, Ithaca, New York, USA
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25
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Rahman MA, Hannan MA, Dash R, Rahman MDH, Islam R, Uddin MJ, Sohag AAM, Rahman MH, Rhim H. Phytochemicals as a Complement to Cancer Chemotherapy: Pharmacological Modulation of the Autophagy-Apoptosis Pathway. Front Pharmacol 2021; 12:639628. [PMID: 34025409 PMCID: PMC8138161 DOI: 10.3389/fphar.2021.639628] [Citation(s) in RCA: 77] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2020] [Accepted: 03/18/2021] [Indexed: 12/11/2022] Open
Abstract
Bioactive plant derived compounds are important for a wide range of therapeutic applications, and some display promising anticancer properties. Further evidence suggests that phytochemicals modulate autophagy and apoptosis, the two crucial cellular pathways involved in the underlying pathobiology of cancer development and regulation. Pharmacological targeting of autophagy and apoptosis signaling using phytochemicals therefore offers a promising strategy that is complementary to conventional cancer chemotherapy. In this review, we sought to highlight the molecular basis of the autophagic-apoptotic pathway to understand its implication in the pathobiology of cancer, and explore this fundamental cellular process as a druggable anticancer target. We also aimed to present recent advances and address the limitations faced in the therapeutic development of phytochemical-based anticancer drugs.
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Affiliation(s)
- Md. Ataur Rahman
- Center for Neuroscience, Korea Institute of Science and Technology (KIST), Seoul, South Korea
- Global Biotechnology & Biomedical Research Network (GBBRN), Department of Biotechnology and Genetic Engineering, Faculty of Biological Sciences, Islamic University, Kushtia, Bangladesh
| | - Md. Abdul Hannan
- Department of Anatomy, Dongguk University College of Medicine, Gyeongju, South Korea
- Department of Biochemistry and Molecular Biology, Bangladesh Agricultural University, Mymensingh, Bangladesh
| | - Raju Dash
- Department of Anatomy, Dongguk University College of Medicine, Gyeongju, South Korea
| | - MD. Hasanur Rahman
- Department of Biotechnology and Genetic Engineering, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj, Bangladesh
- Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul, South Korea
| | - Rokibul Islam
- Department of Biotechnology and Genetic Engineering, Faculty of Biological Sciences, Islamic University, Kushtia, Bangladesh
- Department of Biochemistry, College of Medicine, Hallym University, Chuncheon-si, South Korea
| | - Md Jamal Uddin
- ABEx Bio-Research Center, Dhaka, Bangladesh
- Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul, South Korea
| | - Abdullah Al Mamun Sohag
- Department of Biochemistry and Molecular Biology, Bangladesh Agricultural University, Mymensingh, Bangladesh
| | - Md. Habibur Rahman
- Department of Global Medical Science, Wonju College of Medicine, Yonsei University, Seoul, South Korea
| | - Hyewhon Rhim
- Center for Neuroscience, Korea Institute of Science and Technology (KIST), Seoul, South Korea
- Division of Bio-Medical Science and Technology, KIST School, Korea University of Science and Technology (UST), Seoul, South Korea
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Sarvizadeh M, Hasanpour O, Naderi Ghale-Noie Z, Mollazadeh S, Rezaei M, Pourghadamyari H, Masoud Khooy M, Aschner M, Khan H, Rezaei N, Shojaie L, Mirzaei H. Allicin and Digestive System Cancers: From Chemical Structure to Its Therapeutic Opportunities. Front Oncol 2021; 11:650256. [PMID: 33987085 PMCID: PMC8111078 DOI: 10.3389/fonc.2021.650256] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Accepted: 02/10/2021] [Indexed: 12/24/2022] Open
Abstract
Digestive system cancer tumors are one of the major causes of cancer-related fatalities; the vast majority of them are colorectal or gastric malignancies. Epidemiological evidence confirmed that allium-containing food, such as garlic, reduces the risk of developing malignancies. Among all compounds in garlic, allicin has been most researched, as it contains sulfur and produces many second degradation compounds, such as sulfur dioxide, diallyl sulfide (DAS), diallyl trisulfide (DATS), and diallyl disulfide (DADS) in the presence of enzymatic reactions in gastric juice. These substances have shown anti-inflammatory, antidiabetic, antihypertensive, antifungal, antiviral, antibacterial, and anticancer efficacy, including gastrointestinal (GI) cancers, leukemia, and skin cancers. Herein, we summarize the therapeutic potential of allicin in the treatment of GI cancers.
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Affiliation(s)
- Mahshad Sarvizadeh
- Nutrition and Endocrine Research Centre, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Omid Hasanpour
- School of Paramedicine, Kashan University of Medical Sciences, Kashan, Iran
| | | | - Samaneh Mollazadeh
- Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran
| | - Mohammad Rezaei
- Department of Diabetes, Obesity and Metabolism, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | - Hossein Pourghadamyari
- Department of Clinical Biochemistry, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | | | - Michael Aschner
- Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, United States
| | - Haroon Khan
- Department of Pharmacy, Abdul Wali Khan University, Mardan, Pakistan
| | - Nima Rezaei
- Department of Medical Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
- Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Layla Shojaie
- Department of Medicine, Research Center for Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
| | - Hamed Mirzaei
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
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Wang M, Liu Z, Huang X, Chen Y, Wang Y, Kong J, Yang Y, Yu C, Li J, Wang X, Wang H. Dual-target platinum(IV) complexes exhibit antiproliferative activity through DNA damage and induce ER-stress-mediated apoptosis in A549 cells. Bioorg Chem 2021; 110:104741. [PMID: 33647739 DOI: 10.1016/j.bioorg.2021.104741] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 01/30/2021] [Accepted: 02/08/2021] [Indexed: 12/11/2022]
Abstract
Platinum(II)-based chemotherapeutics are commonly used to treat various types of solid tumors, such as lung cancers. However, these compounds can cause serious side effects, including nephrotoxicity and ototoxicity, which affect the quality of life of patients. In our work, four novel dual target platinum(IV) complexes were designed and synthesized. In vitro results indicated that the title platinum(IV) complexes exhibited effective antitumor activities against the tested cancer cells and had lower toxicity and resistance factors than oxaliplatin and cisplatin. Further mechanistic experiments demonstrated that complex 11 accumulated in mitochondria and induced an elevation in ROS and an ER stress response via mitochondrial dysfunction. Notably, complex 11 significantly modulated the expression levels of proapoptosis proteins including cleaved-Caspase-3, Bax, and p53, and decreased the level of the prosurvival protein Bcl-2. Together, these results suggested that complex 11 might be a potential lead compound for future cancer therapy due to its potency and selectivity.
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Affiliation(s)
- Meng Wang
- Jiangsu Key Laboratory of Regional Resource Exploitation and Medicinal Research, and National & Local Joint Engineering Research Center for Mineral Salt Deep Utilization, Huaiyin Institute of Technology, Huaian 223003, China
| | - Zhikun Liu
- Jiangsu Province Hi-Tech Key Laboratory for Biomedical Research, Southeast University, Nanjing 211189, China
| | - Xiaochao Huang
- Jiangsu Key Laboratory of Regional Resource Exploitation and Medicinal Research, and National & Local Joint Engineering Research Center for Mineral Salt Deep Utilization, Huaiyin Institute of Technology, Huaian 223003, China; State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Collaborative Innovation Center For Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences of Guangxi Normal University, Guilin 541004, China.
| | - Yuanhang Chen
- Jiangsu Key Laboratory of Regional Resource Exploitation and Medicinal Research, and National & Local Joint Engineering Research Center for Mineral Salt Deep Utilization, Huaiyin Institute of Technology, Huaian 223003, China
| | - Yanming Wang
- Jiangsu Key Laboratory of Regional Resource Exploitation and Medicinal Research, and National & Local Joint Engineering Research Center for Mineral Salt Deep Utilization, Huaiyin Institute of Technology, Huaian 223003, China
| | - Jing Kong
- Jiangsu Key Laboratory of Regional Resource Exploitation and Medicinal Research, and National & Local Joint Engineering Research Center for Mineral Salt Deep Utilization, Huaiyin Institute of Technology, Huaian 223003, China
| | - Yong Yang
- Jiangsu Key Laboratory of Regional Resource Exploitation and Medicinal Research, and National & Local Joint Engineering Research Center for Mineral Salt Deep Utilization, Huaiyin Institute of Technology, Huaian 223003, China
| | - Chunhao Yu
- Jiangsu Key Laboratory of Regional Resource Exploitation and Medicinal Research, and National & Local Joint Engineering Research Center for Mineral Salt Deep Utilization, Huaiyin Institute of Technology, Huaian 223003, China
| | - Jin Li
- Jiangsu Key Laboratory of Regional Resource Exploitation and Medicinal Research, and National & Local Joint Engineering Research Center for Mineral Salt Deep Utilization, Huaiyin Institute of Technology, Huaian 223003, China
| | - Xu Wang
- Guangxi Key Laboratory of Green Processing of Sugar Resources, College of Biological and Chemical Engineering, Guangxi University of Science and Technology, Liuzhou 545006, China; State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Collaborative Innovation Center For Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences of Guangxi Normal University, Guilin 541004, China.
| | - Hengshan Wang
- State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Collaborative Innovation Center For Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences of Guangxi Normal University, Guilin 541004, China.
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Alami Merrouni I, Elachouri M. Anticancer medicinal plants used by Moroccan people: Ethnobotanical, preclinical, phytochemical and clinical evidence. JOURNAL OF ETHNOPHARMACOLOGY 2021; 266:113435. [PMID: 33022340 DOI: 10.1016/j.jep.2020.113435] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/21/2020] [Revised: 09/23/2020] [Accepted: 09/26/2020] [Indexed: 05/18/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Cancer is a major health problem worldwide. Drugs' side effects and high cost of treatment remain the main limitations of conventional therapy. Nowadays, developing new therapeutic strategies is necessary. Therefore, medicinal plants can be used to promote novel, safe, and potent anticancer drugs through their natural compounds. AIM OF THE STUDY This review aims to provide scientific evidence related to the anticancer activities of medicinal plants used by Moroccan people as well as approving their efficiency as an alternative cancer therapy. METHODS An ethnopharmacological review approach was conducted by analyzing Moroccan published ethnobotanical surveys from 1991 to 2019 and consulting peer-reviewed articles worldwide to investigate the pharmacological, phytochemical, and clinical effects related to the anticancer activities. Plants with anticancer proprieties were classified into four groups: (a) plants only cited as anticancer, (b) plants pharmacologically investigated, (c) plants with bioactive compounds tested as anticancer, and (d) plants clinically investigated. RESULTS A total of 103 plant species belonging to 47 botanical families used by Moroccans to treat cancer have been recorded. Aristolochia fontanesii Boiss. & Reut, Marrubium vulgare L., and Allium sativum L. are the most referred species in Morocco. Medicinal plants used for cancer treatment were classified into four groups: 48 species were used traditionally as anticancer (group a), 41 species pharmacologically investigated for their anticancer activities (group b), 32 plants with bioactive compounds tested against cancer (group c), and eight plants were clinically investigated for their anticancer effects (group d). Out of 82 plants' extracts pharmacologically tested (from plants of group b), only 24 ones show a significant cytotoxic effect. A total of seventy-seven compounds are isolated from plants of group (c). However, only six ones were clinically evaluated, and most of them exhibit a beneficial effect on cancerous patients with few side effects. CONCLUSION Medicinal plants can be a promising candidate for alternative cancer therapy. Nevertheless, it is critical to increasing the clinical trials to confirm their beneficial effect on patients with cancer. Overall, this review can serve as a database for further studies.
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Affiliation(s)
- Ilyass Alami Merrouni
- Laboratory of Physiology, Genetics, and Ethnopharmacology, Faculty of Sciences, Mohammed First University, Oujda, Morocco.
| | - Mostafa Elachouri
- Laboratory of Physiology, Genetics, and Ethnopharmacology, Faculty of Sciences, Mohammed First University, Oujda, Morocco.
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Mosaddeghi P, Eslami M, Farahmandnejad M, Akhavein M, Ranjbarfarrokhi R, Khorraminejad-Shirazi M, Shahabinezhad F, Taghipour M, Dorvash M, Sakhteman A, Zarshenas MM, Nezafat N, Mobasheri M, Ghasemi Y. A systems pharmacology approach to identify the autophagy-inducing effects of Traditional Persian medicinal plants. Sci Rep 2021; 11:336. [PMID: 33431946 PMCID: PMC7801619 DOI: 10.1038/s41598-020-79472-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Accepted: 12/09/2020] [Indexed: 01/29/2023] Open
Abstract
Aging is correlated with several complex diseases, including type 2 diabetes, neurodegeneration diseases, and cancer. Identifying the nature of this correlation and treatment of age-related diseases has been a major subject of both modern and traditional medicine. Traditional Persian Medicine (TPM) embodies many prescriptions for the treatment of ARDs. Given that autophagy plays a critical role in antiaging processes, the present study aimed to examine whether the documented effect of plants used in TPM might be relevant to the induction of autophagy? To this end, the TPM-based medicinal herbs used in the treatment of the ARDs were identified from modern and traditional references. The known phytochemicals of these plants were then examined against literature for evidence of having autophagy inducing effects. As a result, several plants were identified to have multiple active ingredients, which indeed regulate the autophagy or its upstream pathways. In addition, gene set enrichment analysis of the identified targets confirmed the collective contribution of the identified targets in autophagy regulating processes. Also, the protein-protein interaction (PPI) network of the targets was reconstructed. Network centrality analysis of the PPI network identified mTOR as the key network hub. Given the well-documented role of mTOR in inhibiting autophagy, our results hence support the hypothesis that the antiaging mechanism of TPM-based medicines might involve autophagy induction. Chemoinformatics study of the phytochemicals using docking and molecular dynamics simulation identified, among other compounds, the cyclo-trijuglone of Juglans regia L. as a potential ATP-competitive inhibitor of mTOR. Our results hence, provide a basis for the study of TPM-based prescriptions using modern tools in the quest for developing synergistic therapies for ARDs.
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Affiliation(s)
- Pouria Mosaddeghi
- grid.412571.40000 0000 8819 4698Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran ,grid.412571.40000 0000 8819 4698Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, P.O. Box 71345-1583, Shiraz, Iran ,grid.412571.40000 0000 8819 4698Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran ,grid.412571.40000 0000 8819 4698Cellular and Molecular Medicine Student Research Group, School of Medicine, Shiraz University of Medical Science, Shiraz, Iran
| | - Mahboobeh Eslami
- grid.412571.40000 0000 8819 4698Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran ,grid.412571.40000 0000 8819 4698Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, P.O. Box 71345-1583, Shiraz, Iran
| | - Mitra Farahmandnejad
- grid.412571.40000 0000 8819 4698Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran ,grid.412571.40000 0000 8819 4698Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, P.O. Box 71345-1583, Shiraz, Iran ,grid.412571.40000 0000 8819 4698Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran ,grid.412571.40000 0000 8819 4698Cellular and Molecular Medicine Student Research Group, School of Medicine, Shiraz University of Medical Science, Shiraz, Iran
| | - Mahshad Akhavein
- grid.412571.40000 0000 8819 4698Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran ,grid.412571.40000 0000 8819 4698Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, P.O. Box 71345-1583, Shiraz, Iran ,grid.412571.40000 0000 8819 4698Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran ,grid.412571.40000 0000 8819 4698Cellular and Molecular Medicine Student Research Group, School of Medicine, Shiraz University of Medical Science, Shiraz, Iran
| | - Ratin Ranjbarfarrokhi
- grid.412571.40000 0000 8819 4698Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran ,grid.412571.40000 0000 8819 4698Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, P.O. Box 71345-1583, Shiraz, Iran ,grid.412571.40000 0000 8819 4698Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran ,grid.412571.40000 0000 8819 4698Cellular and Molecular Medicine Student Research Group, School of Medicine, Shiraz University of Medical Science, Shiraz, Iran
| | - Mohammadhossein Khorraminejad-Shirazi
- grid.412571.40000 0000 8819 4698Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran ,grid.412571.40000 0000 8819 4698Cellular and Molecular Medicine Student Research Group, School of Medicine, Shiraz University of Medical Science, Shiraz, Iran
| | - Farbod Shahabinezhad
- grid.412571.40000 0000 8819 4698Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran ,grid.412571.40000 0000 8819 4698Cellular and Molecular Medicine Student Research Group, School of Medicine, Shiraz University of Medical Science, Shiraz, Iran
| | - Mohammadjavad Taghipour
- grid.412571.40000 0000 8819 4698Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran ,grid.412571.40000 0000 8819 4698Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, P.O. Box 71345-1583, Shiraz, Iran ,grid.412571.40000 0000 8819 4698Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran ,grid.412571.40000 0000 8819 4698Cellular and Molecular Medicine Student Research Group, School of Medicine, Shiraz University of Medical Science, Shiraz, Iran
| | - Mohammadreza Dorvash
- grid.412571.40000 0000 8819 4698Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran ,grid.412571.40000 0000 8819 4698Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran ,grid.412571.40000 0000 8819 4698Cellular and Molecular Medicine Student Research Group, School of Medicine, Shiraz University of Medical Science, Shiraz, Iran
| | - Amirhossein Sakhteman
- grid.412571.40000 0000 8819 4698Department of Medicinal Chemistry, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran ,grid.9668.10000 0001 0726 2490Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland
| | - Mohammad M. Zarshenas
- grid.412571.40000 0000 8819 4698Department of Phytopharmaceuticals (Traditional Pharmacy), School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran ,grid.412571.40000 0000 8819 4698Medicinal Plants Processing Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Navid Nezafat
- grid.412571.40000 0000 8819 4698Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran ,grid.412571.40000 0000 8819 4698Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, P.O. Box 71345-1583, Shiraz, Iran
| | - Meysam Mobasheri
- grid.472338.9Department of Biotechnology, Faculty of Advanced Sciences and Technology, Tehran Islamic Azad University of Medical Sciences, Tehran, Iran ,Iranian Institute of New Sciences (IINS), Tehran, Iran
| | - Younes Ghasemi
- grid.412571.40000 0000 8819 4698Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran ,grid.412571.40000 0000 8819 4698Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, P.O. Box 71345-1583, Shiraz, Iran
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Deesrisak K, Chatupheeraphat C, Roytrakul S, Anurathapan U, Tanyong D. Autophagy and apoptosis induction by sesamin in MOLT-4 and NB4 leukemia cells. Oncol Lett 2020; 21:32. [PMID: 33262824 PMCID: PMC7693381 DOI: 10.3892/ol.2020.12293] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2020] [Accepted: 10/16/2020] [Indexed: 12/24/2022] Open
Abstract
Sesamin, the major furofuran lignan found in the seeds of Sesamum indicum L., has been investigated for its various medicinal properties. In the present study, the anti-leukemic effects of sesamin and its underlying mechanisms were investigated in MOLT-4 and NB4 acute leukemic cells. Leukemic cells were treated with various concentrations of sesamin. Cell viability was determined using an MTT assay. Flow cytometry using Annexin V-FITC/PI staining and anti-LC3/FITC antibodies was applied to detect the level of apoptosis and autophagy, respectively. Reverse transcription-quantitative PCR was performed to examine the alterations in the mRNA expression of apoptotic and autophagic genes. In addition, bioinformatics tools were used to predict the possible interactions between sesamin and its targets. The results revealed that sesamin inhibited MOLT-4 and NB4 cell proliferation in a dose-dependent manner. In addition, sesamin induced both apoptosis and autophagy. In sesamin-treated cells, the gene expression levels of caspase 3 and unc-51 like autophagy activating kinase 1 (ULK1) were upregulated, while those of mTOR were downregulated compared with in the control. Notably, the protein-chemical interaction network indicated that caspase 3, mTOR and ULK1 were the essential factors involved in the effects of sesamin treatment, as with anticancer agents, such as rapamycin, AZD8055, Torin1 and 2. Overall, the findings of the present study suggested that sesamin inhibited MOLT-4 and NB4 cell proliferation, and induced apoptosis and autophagy through the regulation of caspase 3 and mTOR/ULK1 signaling, respectively.
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Affiliation(s)
- Kamolchanok Deesrisak
- Department of Clinical Microscopy, Faculty of Medical Technology, Mahidol University, Nakhon Pathom 73170, Thailand
| | - Chawalit Chatupheeraphat
- Department of Clinical Microscopy, Faculty of Medical Technology, Mahidol University, Nakhon Pathom 73170, Thailand
| | - Sittiruk Roytrakul
- Proteomics Research Laboratory, National Center for Genetic Engineering and Biotechnology, Thailand Science Park, Pathum Thani 12120, Thailand
| | - Usanarat Anurathapan
- Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand
| | - Dalina Tanyong
- Department of Clinical Microscopy, Faculty of Medical Technology, Mahidol University, Nakhon Pathom 73170, Thailand
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Mandlik DS, Mandlik SK. Herbal and Natural Dietary Products: Upcoming Therapeutic Approach for Prevention and Treatment of Hepatocellular Carcinoma. Nutr Cancer 2020; 73:2130-2154. [PMID: 33073617 DOI: 10.1080/01635581.2020.1834591] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The most common tumor linked with elevated death rates is considered the hepatocellular carcinoma (HCC), sometimes called the malignant hepatoma. The initiation and progression of HCC are triggered by multiple factors like long term alcohol consumption, metabolic disorders, fatty liver disease, hepatitis B and C infection, age, and oxidative stress. Sorafenib is the merely US Food and Drug Administration (FDA)-approved drug used to treat HCC. Several treatment methods are available for HCC therapy such as chemotherapy, immunotherapy and adjuvant therapy but they often lead to several side effects. Yet these treatment methods are not entirely adequate due to the increasing resistance to the drug and their toxicity. Many natural products help to prevent and treat HCC. A variety of pathways are associated with the prevention and treatment of HCC with herbal products and their active components. Accumulating research shows that certain natural dietary compounds are possible source of hepatic cancer prevention and treatments, such as black currant, strawberries, plum, grapes, pomegranate, cruciferous crops, tomatoes, French beans, turmeric, garlic, ginger, asparagus, and many more. Such a dietary natural products and their active constituents may prevent the production and advancement of liver cancer in many ways such as guarding against liver carcinogens, improving the effectiveness of chemotherapeutic medications, inhibiting the growth, metastasis of tumor cells, reducing oxidative stress, and chronic inflammation. The present review article represents hepatic carcinoma etiology, role of herbal products, their active constituents, and dietary natural products for the prevention and treatment of HCC along with their possible mechanisms of action.
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Affiliation(s)
- Deepa S Mandlik
- Department of Pharmacology, Bharat Vidyapeeth (Deemed to be University), Poona College of Pharmacy, Pune, Maharashtra, India
| | - Satish K Mandlik
- Department of Pharmaceutics, Sinhgad College of Pharmacy, Pune, Maharashtra, India
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Gökalp F. The investigation of the healing effect of active ingredients in traditional medicinal plants on lung cancer. Med Oncol 2020; 37:102. [PMID: 33057857 DOI: 10.1007/s12032-020-01428-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2020] [Accepted: 10/03/2020] [Indexed: 10/23/2022]
Abstract
The healing effect of herbal active compounds on lung cancer has been recently investigated. Lung cancer is one of the leading types of cancer. The causes and prevention of lung cancer diagnosis have an important role as the inhibition of proteins in the initial treatment of the disease. The docking score was used to investigate the effect of some active compounds in traditional medicinal plants. The use of widespread medicinal plants and determination of active substances reveal the importance of docking studies in choosing the right active substance in a short time. The inhibition of essentially active compounds on lung cancer has been an important condition as the traditional medicinal plants that are rich in active substance and direct the experimental studies. In this study, the effects of the active ingredients in traditional food supplements used in many countries on the lung cancer were calculated based on the drugs used as standard. It will be hope that these active substances with high healing effects will be tested in the clinical field and turned into drugs.
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Affiliation(s)
- Faik Gökalp
- Science Education, Department of Mathematics and Science Education, Faculty of Education, Kırıkkale University, 71450, Yahşihan/Kırıkkale, Turkey.
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Chen X, Li H, Xu W, Huang K, Zhai B, He X. Self-Assembling Cyclodextrin-Based Nanoparticles Enhance the Cellular Delivery of Hydrophobic Allicin. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2020; 68:11144-11150. [PMID: 32876450 DOI: 10.1021/acs.jafc.0c01900] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
Most chemotherapeutics are hydrophobic molecules and need to be converted into hydrophilic formulations before administration. To address this issue, a novel cyclodextrin-based nanoparticle was proposed as a versatile carrier for cellular delivery of hydrophobic molecules. First, the effect of the polylysine (PL)/NH2-β-cyclodextrin (NH2-β-CD) ratio on particle size and encapsulation efficiency in prepared complexes was investigated. Subsequently, transmission electron microscopy images showed that the sizes of PL/NH2-β-CD nanoparticles ranging from 10 to 260 nm decreased with the reduction in the PL/NH2-β-CD ratio, which was completely consistent with the findings of size distributions. At a PL/NH2-β-CD ratio of 10, the surface charge on the PL/NH2-β-CD nanoparticle was maximized at (+52.8 mV), and encapsulation efficiency was optimal (47.2%), which revealed a great advantage in delivery of hydrophobic allicin. In addition, the positive charge of PL chains facilitated the cellular uptake of the PL/NH2-β-CD-DOX by interacting with the negatively charged cell membrane. Conclusively, this study suggests that the combination of allicin and PL/NH2-β-CD nanoparticles acting on the S and G2/M phases in cell cycle regulation induces apoptosis and exhibits substantial application in killing cancer cells.
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Affiliation(s)
- Xu Chen
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science & Nutritional Engineering, China Agricultural University, Beijing 100083, China
- Key Laboratory of Safety Assessment of Genetically Modified Organism (Food Safety), Ministry of Agriculture, Beijing 100083, China
| | - Hongyu Li
- Key Laboratory of Safety Assessment of Genetically Modified Organism (Food Safety), Ministry of Agriculture, Beijing 100083, China
| | - Wentao Xu
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science & Nutritional Engineering, China Agricultural University, Beijing 100083, China
- Key Laboratory of Safety Assessment of Genetically Modified Organism (Food Safety), Ministry of Agriculture, Beijing 100083, China
| | - Kunlun Huang
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science & Nutritional Engineering, China Agricultural University, Beijing 100083, China
- Key Laboratory of Safety Assessment of Genetically Modified Organism (Food Safety), Ministry of Agriculture, Beijing 100083, China
| | - Baiqiang Zhai
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science & Nutritional Engineering, China Agricultural University, Beijing 100083, China
| | - Xiaoyun He
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science & Nutritional Engineering, China Agricultural University, Beijing 100083, China
- Key Laboratory of Safety Assessment of Genetically Modified Organism (Food Safety), Ministry of Agriculture, Beijing 100083, China
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34
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Zhao Q, Peng C, Zheng C, He XH, Huang W, Han B. Recent Advances in Characterizing Natural Products that Regulate Autophagy. Anticancer Agents Med Chem 2020; 19:2177-2196. [PMID: 31749434 DOI: 10.2174/1871520619666191015104458] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2018] [Revised: 11/16/2018] [Accepted: 08/26/2019] [Indexed: 02/07/2023]
Abstract
Autophagy, an intricate response to nutrient deprivation, pathogen infection, Endoplasmic Reticulum (ER)-stress and drugs, is crucial for the homeostatic maintenance in living cells. This highly regulated, multistep process has been involved in several diseases including cardiovascular and neurodegenerative diseases, especially in cancer. It can function as either a promoter or a suppressor in cancer, which underlines the potential utility as a therapeutic target. In recent years, increasing evidence has suggested that many natural products could modulate autophagy through diverse signaling pathways, either inducing or inhibiting. In this review, we briefly introduce autophagy and systematically describe several classes of natural products that implicated autophagy modulation. These compounds are of great interest for their potential activity against many types of cancer, such as ovarian, breast, cervical, pancreatic, and so on, hoping to provide valuable information for the development of cancer treatments based on autophagy.
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Affiliation(s)
- Qian Zhao
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu University of Traditional Chinese Medicine, 1166 Liutai Avenue, Chengdu 611137, China
| | - Cheng Peng
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu University of Traditional Chinese Medicine, 1166 Liutai Avenue, Chengdu 611137, China
| | - Chuan Zheng
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu University of Traditional Chinese Medicine, 1166 Liutai Avenue, Chengdu 611137, China
| | - Xiang-Hong He
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu University of Traditional Chinese Medicine, 1166 Liutai Avenue, Chengdu 611137, China
| | - Wei Huang
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu University of Traditional Chinese Medicine, 1166 Liutai Avenue, Chengdu 611137, China
| | - Bo Han
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu University of Traditional Chinese Medicine, 1166 Liutai Avenue, Chengdu 611137, China.,The RNA Institute, University at Albany, State University of New York, Albany, NY 12222, United States
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Subramanian MS, Nandagopal MS G, Amin Nordin S, Thilakavathy K, Joseph N. Prevailing Knowledge on the Bioavailability and Biological Activities of Sulphur Compounds from Alliums: A Potential Drug Candidate. Molecules 2020; 25:molecules25184111. [PMID: 32916777 PMCID: PMC7570905 DOI: 10.3390/molecules25184111] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Revised: 08/15/2020] [Accepted: 08/23/2020] [Indexed: 12/13/2022] Open
Abstract
Allium sativum (garlic) is widely known and is consumed as a natural prophylactic worldwide. It produces more than 200 identified chemical compounds, with more than 20 different kinds of sulfide compounds. The sulfide compounds particularly are proven to contribute to its various biological roles and pharmacological properties such as antimicrobial, antithrombotic, hypoglycemic, antitumour, and hypolipidemic. Therefore, it is often referred as disease-preventive food. Sulphur-containing compounds from A. sativum are derivatives of S-alkenyl-l-cysteine sulfoxides, ajoene molecules, thiosulfinates, sulfides, and S-allylcysteine. This review presents an overview of the water-soluble and oil-soluble sulphur based phytochemical compounds present in garlic, highlighting their mechanism of action in treating various health conditions. However, its role as a therapeutic agent should be extensively studied as it depends on factors such as the effective dosage and the suitable method of preparation.
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Affiliation(s)
- Murugan Sesha Subramanian
- Department of Medical Microbiology and Parasitology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Malaysia; (M.S.S.); (S.A.N.)
| | - Giri Nandagopal MS
- Department of Mechanical Engineering, Indian Institute of Technology, Kharagpur 721302, India;
| | - Syafinaz Amin Nordin
- Department of Medical Microbiology and Parasitology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Malaysia; (M.S.S.); (S.A.N.)
| | - Karuppiah Thilakavathy
- Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Malaysia;
| | - Narcisse Joseph
- Department of Medical Microbiology and Parasitology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Malaysia; (M.S.S.); (S.A.N.)
- Correspondence:
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Forouzanfar F, Mousavi SH. Targeting Autophagic Pathways by Plant Natural Compounds in Cancer Treatment. Curr Drug Targets 2020; 21:1237-1249. [PMID: 32364070 DOI: 10.2174/1389450121666200504072635] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2019] [Revised: 02/26/2020] [Accepted: 03/19/2020] [Indexed: 12/29/2022]
Abstract
Nowadays, natural compounds of plant origin with anticancer effects have gained more attention because of their clinical safety and broad efficacy profiles. Autophagy is a multistep lysosomal degradation pathway that may have a unique potential for clinical benefit in the setting of cancer treatment. To retrieve articles related to the study, the databases of Google Scholar, Web of sciences, Medline and Scopus, using the following keywords: Autophagic pathways; herbal medicine, oncogenic autophagic pathways, tumor-suppressive autophagic pathways, and cancer were searched. Although natural plant compounds such as resveratrol, curcumin, oridonin, gossypol, and paclitaxel have proven anticancer potential via autophagic signaling pathways, there is still a great need to find new natural compounds and investigate the underlying mechanisms, to facilitate their clinical use as potential anticancer agents through autophagic induction.
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Affiliation(s)
- Fatemeh Forouzanfar
- Neuroscience Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Seyed Hadi Mousavi
- Medical Toxicology Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
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Țigu AB, Toma VA, Moț AC, Jurj A, Moldovan CS, Fischer-Fodor E, Berindan-Neagoe I, Pârvu M. The Synergistic Antitumor Effect of 5-Fluorouracil Combined with Allicin against Lung and Colorectal Carcinoma Cells. Molecules 2020; 25:molecules25081947. [PMID: 32331446 PMCID: PMC7221923 DOI: 10.3390/molecules25081947] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2020] [Revised: 04/20/2020] [Accepted: 04/21/2020] [Indexed: 12/19/2022] Open
Abstract
5-fluorouracil (5-FU) is an anticancer drug used to inhibit the proliferation of many different tumor cells. Since severe events are associated with this compound, its combination with different anticancer drugs or adjuvants would allow the use of a significantly lower dose of 5-FU. In this study, we highlighted that the combination of allicin with 5-FU inhibited the cell migration and proliferation of colorectal and lung cancer cells. 5-FU inhibited cell growth with a similar inhibitory concentration for both normal and tumor cells (~200µM), while allicin showed different inhibitory concentrations. With an IC50 of 8.625 µM, lung cancer cells were the most sensitive to allicin. Compared to 5-FU and allicin single-agent treatments, the co-treatment showed a reduced viability rate, with p < 0.05. The morphological changes were visible on all three cell lines, indicating that the treatment inhibited the proliferation of both normal and tumor cells. We highlighted different cell death mechanisms—apoptosis for lung cancer and a non-apoptotic cell death for colorectal cancer. The synergistic antitumor effect of 5-FU combined with allicin was visible against lung and colorectal carcinoma cells. Better results were obtained when a lower concentration of 5-FU was combined with allicin than the single-agent treatment at IC50.
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Affiliation(s)
- Adrian Bogdan Țigu
- MedFuture Research Center for Advanced Medicine, University of Medicine and Pharmacy “Iuliu Hatieganu”, 400349 Cluj-Napoca, Romania; (A.B.Ț.); (C.S.M.); (E.F.-F.); (I.B.-N.)
- Faculty of Biology and Geology, Babeș-Bolyai University, 42 Republicii Street, 400015 Cluj-Napoca, Romania;
| | - Vlad-Alexandru Toma
- Faculty of Biology and Geology, Babeș-Bolyai University, 42 Republicii Street, 400015 Cluj-Napoca, Romania;
- Institute of Biological Research Cluj-Napoca, branch of NIRDBS Bucuresti, 400113 Cluj-Napoca, Romania
- Department of Molecular and Biomolecular Physics, National Institute for R&D of Isotopic and MolecularTechnologies, 67-103 Donat, 400293 Cluj-Napoca, Romania
| | - Augustin Cătălin Moț
- Department of Chemistry, Faculty of Chemistry and Chemical Engineering, Babes-Bolyai University,11 Arany Janos Street, 400028 Cluj-Napoca, Romania;
| | - Ancuța Jurj
- The Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400028 Cluj-Napoca, Romania;
| | - Cristian Silviu Moldovan
- MedFuture Research Center for Advanced Medicine, University of Medicine and Pharmacy “Iuliu Hatieganu”, 400349 Cluj-Napoca, Romania; (A.B.Ț.); (C.S.M.); (E.F.-F.); (I.B.-N.)
- The Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400028 Cluj-Napoca, Romania;
| | - Eva Fischer-Fodor
- MedFuture Research Center for Advanced Medicine, University of Medicine and Pharmacy “Iuliu Hatieganu”, 400349 Cluj-Napoca, Romania; (A.B.Ț.); (C.S.M.); (E.F.-F.); (I.B.-N.)
- Department of Radiobiology and Tumor Biology, the Oncology Institute “Prof Dr Ion Chiricuta”, 400028 Cluj-Napoca, Romania
| | - Ioana Berindan-Neagoe
- MedFuture Research Center for Advanced Medicine, University of Medicine and Pharmacy “Iuliu Hatieganu”, 400349 Cluj-Napoca, Romania; (A.B.Ț.); (C.S.M.); (E.F.-F.); (I.B.-N.)
- The Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400028 Cluj-Napoca, Romania;
- Department of Functional Genomics and Experimental Pathology, the Oncology Institute “Prof Dr Ion Chiricuta”, 400028 Cluj-Napoca, Romania
| | - Marcel Pârvu
- Faculty of Biology and Geology, Babeș-Bolyai University, 42 Republicii Street, 400015 Cluj-Napoca, Romania;
- Correspondence:
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Almatroodi SA, Alsahli MA, Almatroudi A, Rahmani AH. Garlic and its Active Compounds: A Potential Candidate in The Prevention of Cancer by Modulating Various Cell Signalling Pathways. Anticancer Agents Med Chem 2020; 19:1314-1324. [PMID: 30963982 DOI: 10.2174/1871520619666190409100955] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2019] [Revised: 03/07/2019] [Accepted: 03/15/2019] [Indexed: 12/17/2022]
Abstract
BACKGROUND Cancer is a multi-factorial disease including alterations in the cell signalling pathways. Currently, several drugs are in use to treat cancer but such drugs show negative side effects on normal cells and cause severe toxicity. METHODS The current research is mainly focused on medicinal plants with potential therapeutic efficacy in the treatment of cancer without any adverse effects on normal cells. In this regard, garlic and its active compounds including diallyl sulfide, diallyl trisulfide, ajoene, and allicin have been established to suppress the growth of cancer and killing of cancer cells. RESULT The review focuses on garlic and its active compounds chemopreventive effect through modulating various cell signalling pathways. Additionally, garlic and its active compound were established to induce cell cycle arrest at the G0/G1 phase and G2/M phases in cancer cells, increase the expression of tumor suppressor genes, inhibit the angiogenesis process, induction of apoptosis and modulation of various other genetic pathways. CONCLUSION This review sketches the diverse chemopreventive activities of garlic and their active ingredients in the management of cancer mainly focusing on cell signalling pathways.
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Affiliation(s)
- Saleh A Almatroodi
- Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraidah, Saudi Arabia
| | - Mohammed A Alsahli
- Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraidah, Saudi Arabia
| | - Ahmad Almatroudi
- Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraidah, Saudi Arabia
| | - Arshad H Rahmani
- Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraidah, Saudi Arabia
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Panyod S, Wu WK, Lu KH, Liu CT, Chu YL, Ho CT, Hsiao WLW, Lai YS, Chen WC, Lin YE, Lin SH, Wu MS, Sheen LY. Allicin Modifies the Composition and Function of the Gut Microbiota in Alcoholic Hepatic Steatosis Mice. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2020; 68:3088-3098. [PMID: 32050766 DOI: 10.1021/acs.jafc.9b07555] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
The intestinal microbiome plays an important role in the pathogenesis of liver diseases. Alcohol intake induces gut microbiota dysbiosis and alters its function. This study investigated the antibiotic effect of allicin in mice with hepatic steatosis. Male C57BL/6 mice were administered an ethanol diet supplemented with allicin (5 and 20 mg/(kg bw day)) for 4 weeks. Allicin modified the gut microbiota composition. Cecal microbiota exhibited a positive correlation with alcohol and hepatic triacylglycerol, but were suppressed with allicin. Ethanol diet with 5 mg of allicin induced a lower intestinal permeability compared to the ethanol diet alone. Allicin mediated the lipopolysaccharide (LPS)-CD14-toll-like receptor 4 (TLR4)-induced hepatic inflammation pathway by reducing LPS, CD14, TLR4, and pro-inflammatory cytokines-tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. However, hepatic inflammation primarily resulted from alcohol toxicity rather than LPS production in the gut. The prediction of functional profiles from metagenomic 16S ribosomal RNA (rRNA) data revealed different functional profiles in each group. The predicted aldehyde dehydrogenase tended to increase in alcoholic mice administered allicin. The predicted LPS-related pathway and LPS biosynthesis protein results exhibited a similar trend as plasma LPS levels. Thus, alcohol and allicin intake shapes the gut microbiota and its functional profile and improves the CD14-TLR4 pathway to alleviate inflammation in the liver.
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Affiliation(s)
- Suraphan Panyod
- Institute of Food Science and Technology, National Taiwan University, Taipei 10617, Taiwan
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei 10617, Taiwan
| | - Wei-Kai Wu
- Institute of Food Science and Technology, National Taiwan University, Taipei 10617, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital Bei-Hu Branch, Taipei 10800, Taiwan
| | - Kuan-Hung Lu
- Institute of Food Science and Technology, National Taiwan University, Taipei 10617, Taiwan
| | - Chun-Ting Liu
- Product and Process Research Center, Food Industry Research and Development Institute, Hsinchu 30062, Taiwan
| | - Yung-Lin Chu
- Department of Food Science, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan
| | - Chi-Tang Ho
- Department of Food Science, Rutgers University, New Brunswick, New Jersey 08901, United States
| | - Wen-Luan Wendy Hsiao
- State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau, China
| | - Yi-Syuan Lai
- Department of Hospitality Management, Yu Da University of Science and Technology, Miaoli 36143, Taiwan
| | - Wei-Cheng Chen
- Institute of Food Science and Technology, National Taiwan University, Taipei 10617, Taiwan
| | - Yu-En Lin
- Institute of Food Science and Technology, National Taiwan University, Taipei 10617, Taiwan
| | - Shi-Hang Lin
- Institute of Food Science and Technology, National Taiwan University, Taipei 10617, Taiwan
| | - Ming-Shiang Wu
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei 10617, Taiwan
| | - Lee-Yan Sheen
- Institute of Food Science and Technology, National Taiwan University, Taipei 10617, Taiwan
- Center for Food and Biomolecules, National Taiwan University, Taipei 10617, Taiwan
- National Center for Food Safety Education and Research, National Taiwan University, Taipei 10617, Taiwan
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Zhang Y, Liu X, Ruan J, Zhuang X, Zhang X, Li Z. Phytochemicals of garlic: Promising candidates for cancer therapy. Biomed Pharmacother 2020; 123:109730. [PMID: 31877551 DOI: 10.1016/j.biopha.2019.109730] [Citation(s) in RCA: 77] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Revised: 11/30/2019] [Accepted: 12/04/2019] [Indexed: 12/30/2022] Open
Abstract
Of the numerous health benefits of garlic, the anticancer effect is probably the most noticeable. Observations over the past years have shown that the consumption of garlic in the diet provides strong protection against cancer risk. Previous studies involving garlic phytochemicals have usually focused on the cancer chemopreventive properties, but there is little published evidence showing its therapeutic potential in cancer treatment. In view of the multitargeted carcinoma actions and lack of severe toxicity, some components of garlic are likely to play vital roles in the selective killing of cancer cells. However, the rational design of experimental studies and clinical trials are required to verify this concept. This paper discusses the promises and pitfalls of garlic for the treatment of cancer.
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Affiliation(s)
- Yan Zhang
- Institute of Reproductive Health, Tongji College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
| | - Xingping Liu
- Institute of Reproductive Health, Tongji College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
| | - Jun Ruan
- College of Life Sciences, Central China Normal University, Wuhan 430079, Hubei, China.
| | - Xuan Zhuang
- Department of Urology, The First Affiliated Hospital of Xiamen University, Xiamen 361003, Fujian, China.
| | - Xinzong Zhang
- NHC Key Laboratory of Male Reproduction and Genetics, Family Planning Research Institute of Guangdong Province, Guangzhou 510600, Guangdong, China.
| | - Zhiming Li
- Institute of Reproductive Health, Tongji College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
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Wu H, Li X, Zhang T, Zhang G, Chen J, Chen L, He M, Hao B, Wang C. Overexpression miR-486-3p Promoted by Allicin Enhances Temozolomide Sensitivity in Glioblastoma Via Targeting MGMT. Neuromolecular Med 2020; 22:359-369. [PMID: 32086739 PMCID: PMC7417398 DOI: 10.1007/s12017-020-08592-5] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2019] [Accepted: 02/03/2020] [Indexed: 02/07/2023]
Abstract
Glioblastoma is the most common primary tumor of the central nervous system that develops chemotherapy resistance. Previous studies showed that Allicin could inhibit multiple cancer cells including glioblastoma, but the function of Allicin in glioblastoma is still unclear. Our work aimed to investigate the underlying molecular mechanism. The results showed that miR-486-3p levels were greatly increased in glioblastoma during Allicin treatment. Overexpression of miR-486-3p increased chemosensitivity to temozolomide (TMZ) in vitro and in vivo. O6-methylguanine-DNA methyltransferase (MGMT) was identified as a direct target of miR-486-3p, and miR-486-3p overexpression prevented the protein translation of MGMT. Moreover, overexpression of MGMT restored miR-486-3p-induced chemosensitivity to TMZ. Taken together, our studies revealed that Allicin could upregulate miR-486-3p and enhance TMZ sensitivity in glioblastoma. The results suggested that in the future, Allicin can be used as an adjuvant therapy with TMZ to improve the prognosis of patients, and miR-486-3p may be a potential target for glioblastoma treatment to improve the curative effects.
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Affiliation(s)
- Henggang Wu
- Department of Neurosurgery, Wenrong Hospital of Hengdian, Jinhua, 322118, Zhejiang, China
| | - Xu Li
- Department of Neurosurgery, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310002, Zhejiang, China
| | - Tiehui Zhang
- Department of Neurosurgery, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310002, Zhejiang, China
| | - Guojun Zhang
- Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310011, Zhejiang, China
| | - Jingnan Chen
- Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310011, Zhejiang, China
| | - Li Chen
- Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310011, Zhejiang, China
| | - Min He
- Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310011, Zhejiang, China
| | - Bilie Hao
- Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310011, Zhejiang, China
| | - Cheng Wang
- Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310011, Zhejiang, China.
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42
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Park Y, Lee S, Yoon J, Kim E, Park S. Allicin protects porcine oocytes against damage during aging in vitro. Mol Reprod Dev 2019; 86:1116-1125. [DOI: 10.1002/mrd.23227] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2018] [Accepted: 06/01/2019] [Indexed: 12/27/2022]
Affiliation(s)
- Yun‐Gwi Park
- Stem Cell Research CenterJeju National UniversityJeju Jeju Special Self‐Governing Province Korea
- Faculty of Biotechnology, College of Applied Life SciencesJeju National UniversityJeju Jeju Special Self‐Governing Province Korea
- Mirae Cell BioSeoul Korea
| | - Seung‐Eun Lee
- Stem Cell Research CenterJeju National UniversityJeju Jeju Special Self‐Governing Province Korea
- Faculty of Biotechnology, College of Applied Life SciencesJeju National UniversityJeju Jeju Special Self‐Governing Province Korea
| | - Jae‐Wook Yoon
- Stem Cell Research CenterJeju National UniversityJeju Jeju Special Self‐Governing Province Korea
- Faculty of Biotechnology, College of Applied Life SciencesJeju National UniversityJeju Jeju Special Self‐Governing Province Korea
| | - Eun‐Young Kim
- Stem Cell Research CenterJeju National UniversityJeju Jeju Special Self‐Governing Province Korea
- Faculty of Biotechnology, College of Applied Life SciencesJeju National UniversityJeju Jeju Special Self‐Governing Province Korea
- Mirae Cell BioSeoul Korea
- Byon Co., Ltd.Seoul Korea
| | - Se‐Pill Park
- Stem Cell Research CenterJeju National UniversityJeju Jeju Special Self‐Governing Province Korea
- Faculty of Biotechnology, College of Applied Life SciencesJeju National UniversityJeju Jeju Special Self‐Governing Province Korea
- Mirae Cell BioSeoul Korea
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The Role of Herbal Bioactive Components in Mitochondria Function and Cancer Therapy. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2019; 2019:3868354. [PMID: 31308852 PMCID: PMC6594309 DOI: 10.1155/2019/3868354] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/13/2019] [Revised: 04/27/2019] [Accepted: 06/02/2019] [Indexed: 12/13/2022]
Abstract
Mitochondria are highly dynamic double-membrane organelles which play a well-recognized role in ATP production, calcium homeostasis, oxidation-reduction (redox) status, apoptotic cell death, and inflammation. Dysfunction of mitochondria has long been observed in a number of human diseases, including cancer. Targeting mitochondria metabolism in tumors as a cancer therapeutic strategy has attracted much attention for researchers in recent years due to the essential role of mitochondria in cancer cell growth, apoptosis, and progression. On the other hand, a series of studies have indicated that traditional medicinal herbs, including traditional Chinese medicines (TCM), exert their potential anticancer effects as an effective adjunct treatment for alleviating the systemic side effects of conventional cancer therapies, for reducing the risk of recurrence and cancer mortality and for improving the quality of patients' life. An amazing feature of these structurally diverse bioactive components is that majority of them target mitochondria to provoke cancer cell-specific death program. The aim of this review is to summarize the in vitro and in vivo studies about the role of these herbs, especially their bioactive compounds in the modulation of the disturbed mitochondrial function for cancer therapy.
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Sun P, Huang J, Xu J, Yu N. Efficient and stereoselective synthesis of thiosulfinates from disulfide using cumene hydroperoxide in the presence of titanium-based catalyst systems. SYNTHETIC COMMUN 2019. [DOI: 10.1080/00397911.2019.1590847] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Affiliation(s)
- Pengju Sun
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China
| | | | - Jinyi Xu
- Drug Research Institute, Hisun Group, Taizhou, China
| | - Niefang Yu
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China
- Drug Research Institute, Hisun Group, Taizhou, China
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45
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Autophagy as a molecular target for cancer treatment. Eur J Pharm Sci 2019; 134:116-137. [PMID: 30981885 DOI: 10.1016/j.ejps.2019.04.011] [Citation(s) in RCA: 271] [Impact Index Per Article: 45.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2018] [Revised: 04/04/2019] [Accepted: 04/05/2019] [Indexed: 12/22/2022]
Abstract
Autophagy is an evolutionarily conserved catabolic mechanism, by which eukaryotic cells recycle or degrades internal constituents through membrane-trafficking pathway. Thus, autophagy provides the cells with a sustainable source of biomolecules and energy for the maintenance of homeostasis under stressful conditions such as tumor microenvironment. Recent findings revealed a close relationship between autophagy and malignant transformation. However, due to the complex dual role of autophagy in tumor survival or cell death, efforts to develop efficient treatment strategies targeting the autophagy/cancer relation have largely been unsuccessful. Here we review the two-faced role of autophagy in cancer as a tumor suppressor or as a pro-oncogenic mechanism. In this sense, we also review the shared regulatory pathways that play a role in autophagy and malignant transformation. Finally, anti-cancer therapeutic agents used as either inhibitors or inducers of autophagy have been discussed.
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46
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Salehi B, Zucca P, Orhan IE, Azzini E, Adetunji CO, Mohammed SA, Banerjee SK, Sharopov F, Rigano D, Sharifi-Rad J, Armstrong L, Martorell M, Sureda A, Martins N, Selamoğlu Z, Ahmad Z. Allicin and health: A comprehensive review. Trends Food Sci Technol 2019; 86:502-516. [DOI: 10.1016/j.tifs.2019.03.003] [Citation(s) in RCA: 109] [Impact Index Per Article: 18.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Martel J, Ojcius DM, Ko YF, Chang CJ, Young JD. Antiaging effects of bioactive molecules isolated from plants and fungi. Med Res Rev 2019; 39:1515-1552. [PMID: 30648267 DOI: 10.1002/med.21559] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2018] [Revised: 12/06/2018] [Accepted: 12/08/2018] [Indexed: 12/14/2022]
Affiliation(s)
- Jan Martel
- Center for Molecular and Clinical Immunology, Chang Gung University; Taoyuan Taiwan Republic of China
- Chang Gung Immunology Consortium, Linkou Chang Gung Memorial Hospital; Taoyuan Taiwan, Republic of China
| | - David M. Ojcius
- Center for Molecular and Clinical Immunology, Chang Gung University; Taoyuan Taiwan Republic of China
- Chang Gung Immunology Consortium, Linkou Chang Gung Memorial Hospital; Taoyuan Taiwan, Republic of China
- Department of Biomedical Sciences; University of the Pacific, Arthur Dugoni School of Dentistry; San Francisco California
| | - Yun-Fei Ko
- Chang Gung Immunology Consortium, Linkou Chang Gung Memorial Hospital; Taoyuan Taiwan, Republic of China
- Chang Gung Biotechnology Corporation; Taipei Taiwan Republic of China
- Biochemical Engineering Research Center, Ming Chi University of Technology; New Taipei City Taiwan Republic of China
| | - Chih-Jung Chang
- Center for Molecular and Clinical Immunology, Chang Gung University; Taoyuan Taiwan Republic of China
- Chang Gung Immunology Consortium, Linkou Chang Gung Memorial Hospital; Taoyuan Taiwan, Republic of China
- Department of Medical Biotechnology and Laboratory Science; College of Medicine, Chang Gung University; Taoyuan Taiwan Republic of China
- Research Center of Bacterial Pathogenesis, Chang Gung University; Taoyuan Taiwan Republic of China
- Department of Microbiology and Immunology; College of Medicine, Chang Gung University; Taoyuan Taiwan Republic of China
| | - John D. Young
- Center for Molecular and Clinical Immunology, Chang Gung University; Taoyuan Taiwan Republic of China
- Chang Gung Immunology Consortium, Linkou Chang Gung Memorial Hospital; Taoyuan Taiwan, Republic of China
- Chang Gung Biotechnology Corporation; Taipei Taiwan Republic of China
- Biochemical Engineering Research Center, Ming Chi University of Technology; New Taipei City Taiwan Republic of China
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Lu MC, Li TY, Hsieh YC, Hsieh PC, Chu YL. Chemical evaluation and cytotoxic mechanism investigation of Clinacanthus nutans extract in lymphoma SUP-T1 cells. ENVIRONMENTAL TOXICOLOGY 2018; 33:1229-1236. [PMID: 30188005 DOI: 10.1002/tox.22629] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/08/2018] [Revised: 07/04/2018] [Accepted: 07/16/2018] [Indexed: 06/08/2023]
Abstract
Clinacanthus nutans has been used as herbal medicine with antidiabetic, blood pressure lowering, and diuretic properties in Singapore, Thailand, and Malaysia. The in vitro cellular study showed the chloroform extract possessed significant cytotoxicity against leukemia K562 and lymphoma Raji cells. The clinical study reported that administration of plant could treat or prevent relapse in 12 cancer patients. However, detailed mechanism of the anticancer effects and chemical profiles are not thoroughly studied. The chemical study did show that the acetone extract (MHA) exerted the highest antiproliferative effect on human leukemia MOLT-4 cells and lymphoma SUP-T1 cells in dose-dependent cytotoxicity. We found that the use of MHA increased apoptosis by 4.28%-43.65% and caused disruption of mitochondrial membrane potential (MMP) by 11.79%-26.93%, increased reactive oxygen species (ROS) by 19.54% and increased calcium ion by 233.83%, as demonstrated by annexin-V/PI, JC-1, H2 DCFDA, and Flou-3 staining assays, respectively. MHA-induced ER stress was confirmed by increase expression of CHOP and IRE-1α with western blotting assay. In conclusion, we identified good bioactivity in Clinacanthus nutans and recognize its potential effect on cancer therapy, but further research is needed to determine the use of the plant.
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Affiliation(s)
- Mei-Chin Lu
- Graduate Institute of Marine Biology, National Dong Hwa University, Hualien, Taiwan
| | - Tsung-Yuan Li
- Department of Food Science, Agricultural College, National Pingtung University of Science and Technology, Neipu, Pingtung, Taiwan
| | - Yu-Chun Hsieh
- Institute of Food Science and Technology, National Taiwan University, Taipei, Taiwan
| | - Pao-Chuan Hsieh
- Department of Food Science, Agricultural College, National Pingtung University of Science and Technology, Neipu, Pingtung, Taiwan
| | - Yung-Lin Chu
- International Master's Degree Program in Food Science, International College, National Pingtung University of Science and Technology, Neipu, Pingtung, Taiwan
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Lin CH, Funayama S, Peng SF, Kuo CL, Chung JG. The ethanol extraction of prepared Psoralea corylifolia induces apoptosis and autophagy and alteres genes expression assayed by cDNA microarray in human prostate cancer PC-3 cells. ENVIRONMENTAL TOXICOLOGY 2018; 33:770-788. [PMID: 29667321 DOI: 10.1002/tox.22564] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/18/2017] [Revised: 03/25/2018] [Accepted: 04/01/2018] [Indexed: 06/08/2023]
Abstract
Prostate cancer is the most common male reproductive system cancer. The prevalence of prostate cancer in Europe and the United States is higher than that in the Asian region. However, the treatment of prostate cancer remains unsatisfactory. Psoralea corylifolia has been used to cure this disease as Chinese medicine in the Asian region. In this study, we analyzed the components of ethanol extraction of unprepared and prepared P. corylifolia by HPLC. Psoralen and isopsoralen content from the prepared P. corylifolia is twofold higher than that from unprepared, so we use the prepared extraction in this study. However, the effects of the ethanol extraction of P. corylifolia (PCE) on PC-3 human prostate cancer cells remain unclear. PC-3 cells were treated with PCE for different time periods and cells were examined for cell morphological change and total viable cells by using contrast phase microscopy and flow cytometer, respectively. Results indicated that PCE induced cell morphological changes and cytotoxic effect in PC-3 cells in dose-dependent manners. PCE induced chromatin condensation of PC-3 cells dose-dependently. PCE also induced apoptosis and autophagy in PC-3 by western blotting and acridine orange (AO) staining, respectively. Furthermore, a complementary DNA microarray analysis demonstrated that PCE treatment led to 944 genes upregulation and 872 genes downregulation. For example, the DNA damage-associated gene DNA-damage-inducible transcript 3 (DDIT 3) had a 62.1-fold upregulation and CDK1 2.68-fold downregulation. The differential genes were classified according to the Gene Ontology. Furthermore, GeneGo software was used for the key genes involved and their possible interaction pathways. Those genes were affected by P. corylifolia, which provided information for the understanding of the antiprostate cancer mechanism at the genetic level and provide additional targets for the treatments of human prostate cancer.
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Affiliation(s)
- Chia-Hsin Lin
- Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, 404, Taiwan
| | - Shinji Funayama
- Department of Kampo Pharmaceutical Sciences, Nihon Pharmaceutical University Saitama, Saitama, Japan
| | - Shu-Fen Peng
- Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, 404, Taiwan
| | - Chao-Lin Kuo
- Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, 404, Taiwan
| | - Jing-Gung Chung
- Department of Biological Science and Technology, China Medical University, 404, Taiwan, Taichung
- Department of Biotechnology, Asia University, Taichung, 413, Taiwan
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50
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Moosavi MA, Haghi A, Rahmati M, Taniguchi H, Mocan A, Echeverría J, Gupta VK, Tzvetkov NT, Atanasov AG. Phytochemicals as potent modulators of autophagy for cancer therapy. Cancer Lett 2018; 424:46-69. [PMID: 29474859 DOI: 10.1016/j.canlet.2018.02.030] [Citation(s) in RCA: 80] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2017] [Revised: 02/18/2018] [Accepted: 02/19/2018] [Indexed: 02/07/2023]
Abstract
The dysregulation of autophagy is involved in the pathogenesis of a broad range of diseases, and accordingly universal research efforts have focused on exploring novel compounds with autophagy-modulating properties. While a number of synthetic autophagy modulators have been identified as promising cancer therapy candidates, autophagy-modulating phytochemicals have also attracted attention as potential treatments with minimal side effects. In this review, we firstly highlight the importance of autophagy and its relevance in the pathogenesis and treatment of cancer. Subsequently, we present the data on common phytochemicals and their mechanism of action as autophagy modulators. Finally, we discuss the challenges associated with harnessing the autophagic potential of phytochemicals for cancer therapy.
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Affiliation(s)
- Mohammad Amin Moosavi
- Department of Molecular Medicine, National Institute of Genetic Engineering and Biotechnology, P.O Box:14965/161, Tehran, Iran.
| | - Atousa Haghi
- Young Researchers & Elite Club, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran
| | - Marveh Rahmati
- Cancer Biology Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Hiroaki Taniguchi
- Institute of Genetics and Animal Breeding of the Polish Academy of Sciences, 05-552 Jastrzebiec, Poland
| | - Andrei Mocan
- Department of Pharmaceutical Botany, "Iuliu Haţieganu" University of Medicine and Pharmacy, Gheorghe Marinescu 23 Street, 400337 Cluj-Napoca, Romania
| | - Javier Echeverría
- Facultad de Química y Biología, Universidad de Santiago de Chile, Casilla 40, Correo 33, Santiago 9170022, Chile
| | - Vijai K Gupta
- Department of Chemistry and Biotechnology, ERA Chair of Green Chemistry, Tallinn University of Technology, 12618 Tallinn, Estonia
| | - Nikolay T Tzvetkov
- Pharmaceutical Institute, University of Bonn, An der Immenburg 4, 53121 Bonn, Germany; NTZ Lab Ltd., Krasno Selo 198, Sofia 1618, Bulgaria
| | - Atanas G Atanasov
- Institute of Genetics and Animal Breeding of the Polish Academy of Sciences, 05-552 Jastrzebiec, Poland; Department of Pharmacognosy, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria.
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