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Chang IY, Boo HJ, Hyun JW, Yoon SP. The feasible role of soluble E‑cadherin in spheroidogenesis of HCT116 colorectal cancer cells, a candidate biomarker for liquid biopsy. Oncol Lett 2025; 29:245. [PMID: 40182609 PMCID: PMC11967162 DOI: 10.3892/ol.2025.14991] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Accepted: 02/21/2025] [Indexed: 04/05/2025] Open
Abstract
Although E-cadherin is known as a tumor suppressor via its effects on cell to cell adhesion, the effects of E-cadherin on malignant transformation have not yet been thoroughly investigated. In the present study, after malignant transformation was induced by spheroid formation in a fetal bovine serum-supplemented environment, the effects of soluble E-cadherin on the spheroidogenesis of colorectal cancer cells were investigated. E-cadherin knock-out (KO) was performed in HCT116 cells, targeting exon 3 of the CDH1 gene. A cell viability assay was performed to determine the proliferation and viability of wild type and CDH1 KO HCT116 cells after treatment with anticancer drugs. Spheroidogenesis was compared with or without exogenous E-cadherin, antibody against the ectodomain of E-cadherin (DECMA-1) and PD98059 treatment. In addition, morphometry, immunocytochemistry and western blotting were performed. Soluble E-cadherin in culture media was measured using an enzyme-linked immunosorbent assay. Firstly, CDH1 KO was confirmed by western blotting. Notably, the proliferation and viability of cells following treatment with 5-fluorouracil, epidermal growth factor receptor inhibitor and src kinase inhibitor were similar between the cell lines. Exogenous E-cadherin or DECMA-1 treatment did not affect spheroidogenesis, although long-term maintenance was slightly disturbed in CDH1 KO spheroids compared with that in wild type spheroids. In addition, E-cadherin was increased in spheroid culture as compared with that in conventional culture. Soluble E-cadherin was increased in a time-dependent manner, particularly in wild type HCT116 cells. PD98059 inhibited ERK activation and enhanced E-cadherin expression in conventional culture without affecting spheroidogenesis. These results suggested that soluble E-cadherin may be considered as a biomarker for colorectal cancer, although exogenous E-cadherin might not have a further role in malignant transformation.
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Affiliation(s)
- In-Youb Chang
- Department of Anatomy, College of Medicine, Chosun University, Gwangju 61452, Republic of Korea
| | - Hye-Jin Boo
- Jeju Research Center for Natural Medicine, Jeju National University, Jeju 63243, Republic of Korea
| | - Jin Won Hyun
- Jeju Research Center for Natural Medicine, Jeju National University, Jeju 63243, Republic of Korea
| | - Sang-Pil Yoon
- Jeju Research Center for Natural Medicine, Jeju National University, Jeju 63243, Republic of Korea
- Department of Anatomy, College of Medicine, Jeju National University, Jeju 63243, Republic of Korea
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Sameh S, Elissawy AM, Al-Sayed E, Labib RM, Chang HW, Yu SY, Chang FR, Yang SC, Singab ANB. Family Malvaceae: a potential source of secondary metabolites with chemopreventive and anticancer activities supported with in silico pharmacokinetic and pharmacodynamic profiles. Front Pharmacol 2024; 15:1465055. [PMID: 39478959 PMCID: PMC11521888 DOI: 10.3389/fphar.2024.1465055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Accepted: 10/04/2024] [Indexed: 11/02/2024] Open
Abstract
Introduction Cancer is the second most widespread cause of mortality following cardiovascular disorders, and it imposes a heavy global burden. Nowadays, herbal nutraceutical products with a plethora of bioactive metabolites represent a foundation stone for the development of promising chemopreventive and anticancer agents. Certain members of the family Malvaceae have traditionally been employed to relieve tumors. The literature concerning the chemopreventive and anticancer effects of the plant species along with the isolated cytotoxic phytometabolites was reviewed. Based on the findings, comprehensive computational modelling studies were performed to explore the pharmacokinetic and pharmacodynamic profiles of the reported cytotoxic metabolites to present basis for future plant-based anticancer drug discovery. Methods All the available information about the anticancer research in family Malvaceae and its cytotoxic phytometabolites were retrieved from official sources. Extensive search was carried out using the keywords Malvaceae, cancer, cytotoxicity, mechanism and signalling pathway. Pharmacokinetic study was performed on the cytotoxic metabolites using SWISS ADME model. Acute oral toxicity expressed as median lethal dose (LD50) was predicted using Pro Tox 3.0 web tool. The compounds were docked using AutoDock Vina platform against epidermal growth factor receptor (EGFR kinase enzyme) obtained from the Protein Data Bank. Molecular dynamic simulations and MMGBSA calculations were performed using GROMACS 2024.2 and gmx_MMPBSA tool v1.5.2. Results One hundred forty-five articles were eligible in the study. Several tested compounds showed safe pharmacokinetic properties. Also, the molecular docking study showed that the bioactive metabolites possessed agreeable binding affinities to EGFR kinase enzyme. Tiliroside (25), boehmenan (30), boehmenan H (31), and isoquercetin (22) elicited the highest binding affinity toward the enzyme with a score of -10.4, -10.4, -10.2 and -10.1 Kcal/mol compared to the reference drug erlotinib having a binding score equal to -9 Kcal/mol. Additionally, compounds 25 and 31 elicited binding free energies equal to -42.17 and -42.68 Kcal/mol, respectively, comparable to erlotinib. Discussion Overall, the current study presents helpful insights into the pharmacokinetic and pharmacodynamic properties of the reported cytotoxic metabolites belonging to family Malvaceae members. The molecular docking and dynamic simulations results intensify the roles of secondary metabolites from medicinal plants in fighting cancer.
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Affiliation(s)
- Salma Sameh
- Department of Pharmacognosy, Faculty of Pharmacy, Ain-Shams University, Cairo, Egypt
| | - Ahmed M. Elissawy
- Department of Pharmacognosy, Faculty of Pharmacy, Ain-Shams University, Cairo, Egypt
- Center of Drug Discovery Research and Development, Faculty of Pharmacy, Ain-Shams University, Cairo, Egypt
| | - Eman Al-Sayed
- Department of Pharmacognosy, Faculty of Pharmacy, Ain-Shams University, Cairo, Egypt
| | - Rola M. Labib
- Department of Pharmacognosy, Faculty of Pharmacy, Ain-Shams University, Cairo, Egypt
| | - Hsueh-Wei Chang
- Department of Biomedical Science and Environmental Biology, and PhD Program in Life Sciences, College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Szu-Yin Yu
- School of Pharmacy and Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Fang-Rong Chang
- School of Pharmacy and Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shyh-Chyun Yang
- School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Abdel Nasser B. Singab
- Department of Pharmacognosy, Faculty of Pharmacy, Ain-Shams University, Cairo, Egypt
- Center of Drug Discovery Research and Development, Faculty of Pharmacy, Ain-Shams University, Cairo, Egypt
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Miranda BCJ, Tustumi F, Nakamura ET, Shimanoe VH, Kikawa D, Waisberg J. Obesity and Colorectal Cancer: A Narrative Review. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:1218. [PMID: 39202500 PMCID: PMC11355959 DOI: 10.3390/medicina60081218] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Revised: 07/21/2024] [Accepted: 07/24/2024] [Indexed: 09/03/2024]
Abstract
Background and Objectives: Cancer is a multicausal disease, and environmental, cultural, socioeconomic, lifestyle, and genetic factors can influence the risk of developing cancer. Colorectal cancer (CRC) stands as the third most common cancer globally. Some countries have observed a rise in the incidence of CRC, especially among young people. This increase is associated with lifestyle changes over the last few decades, including changes in diet patterns, a sedentary lifestyle, and obesity. Currently, obesity and overweight account for approximately 39% of the world's population and increase the risk of overall mortality of certain cancer types. This study aims to conduct a literature review examining the association between obesity and CRC. Materials and Methods: This narrative review explored the pathophysiological mechanisms, treatment strategies, and challenges related to obesity and CRC. Results: Several studies have established a clear causal relationship between obesity and CRC, showing that individuals with morbid obesity are at a higher risk of developing colorectal cancer. The adipose tissue, particularly the visceral, secretes proinflammatory cytokines, such as TNF-alpha, interleukin-6, and C-reactive protein. Chronic inflammation is closely linked to cancer initiation and progression, with a complex interplay of molecular mechanisms underlying this association. Obesity can complicate the treatment of CRC due to several factors, reducing the therapeutic effectiveness and increasing the risk for adverse events during treatment. Dietary modification, calorie restriction, and other types of weight-control strategies can reduce the risk of CRC development and improve treatment outcomes. Conclusions: Obesity is intricately linked to CRC development and progression, making it a crucial target for intervention, whether through diet therapy, physical exercises, medical therapy, or bariatric surgery.
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Affiliation(s)
- Bárbara Cristina Jardim Miranda
- Department of Surgery, Instituto de Assistência Médica ao Servidor Público Estadual—IAMSPE, Sao Paulo 04029-000, SP, Brazil
- Department of Surgery, Faculdade de Medicina do ABC—FMABC, Santo Andre 09060-870, SP, Brazil
| | - Francisco Tustumi
- Department of Gastroenterology, Faculty of Medicine, Universidade de São Paulo—USP, Sao Paulo 14040-903, SP, Brazil
- Department of Health Sciences, Sociedade Beneficente Israelita Brasileira Albert Einstein, Sao Paulo 05652-900, SP, Brazil
| | - Eric Toshiyuki Nakamura
- Department of Gastroenterology, Faculty of Medicine, Universidade de São Paulo—USP, Sao Paulo 14040-903, SP, Brazil
| | - Victor Haruo Shimanoe
- Department of Gastroenterology, Faculty of Medicine, Universidade de São Paulo—USP, Sao Paulo 14040-903, SP, Brazil
| | - Daniel Kikawa
- Department of Gastroenterology, Faculty of Medicine, Universidade de São Paulo—USP, Sao Paulo 14040-903, SP, Brazil
| | - Jaques Waisberg
- Department of Surgery, Instituto de Assistência Médica ao Servidor Público Estadual—IAMSPE, Sao Paulo 04029-000, SP, Brazil
- Department of Surgery, Faculdade de Medicina do ABC—FMABC, Santo Andre 09060-870, SP, Brazil
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Song X, Sun J, Liu H, Mushtaq A, Huang Z, Li D, Zhang L, Chen F. Lycopene Alleviates Endoplasmic Reticulum Stress in Steatohepatitis through Inhibition of the ASK1-JNK Signaling Pathway. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2024; 72:7832-7844. [PMID: 38544357 DOI: 10.1021/acs.jafc.3c08108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/11/2024]
Abstract
Lycopene has been proven to alleviate nonalcoholic steatohepatitis (NASH), but the precise mechanisms are inadequately elucidated. In this study, we found a previously unknown regulatory effect of lycopene on the apoptosis signal-regulating kinase 1 (ASK1) signaling pathway in both in vivo and in vitro models. Lycopene supplementation (3 and 6 mg/kg/day) exhibited a significant reduction in lipid accumulation, inflammation, and fibrosis of the liver in mice fed with a high-fat/high-cholesterol diet or a methionine-choline-deficient diet. RNA sequencing uncovered that the mitogen-activated protein kinases signaling pathway, which is closely associated with inflammation and endoplasmic reticulum (ER) stress, was significantly downregulated by lycopene. Furthermore, we found lycopene ameliorated ER swelling and decreased the expression levels of ER stress markers (i.e., immunoglobulin heavy chain binding protein, C/EBP homologous protein, and X-box binding protein 1s). Especially, the inositol-requiring enzyme 1α involved in the ASK1 phosphorylation was inhibited by lycopene, resulting in the decline of the subsequent c-Jun N-terminal kinase (JNK) signaling cascade. ASK1 inhibitor DQOP-1 eliminated the lycopene-induced inhibition of the ASK1-JNK pathway in oleic acid and palmitic acid-induced HepG2 cells. Molecular docking further indicated hydrophobic interactions between lycopene and ASK1. Collectively, our research indicates that lycopene can alleviate ER stress and attenuate inflammation cascades and lipid accumulation by inhibiting the ASK1-JNK pathway.
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Affiliation(s)
- Xunyu Song
- College of Food Science and Nutritional Engineering, National Engineering Research Centre for Fruit and Vegetable Processing, Key Laboratory of Fruits and Vegetables Processing, Ministry of Agriculture; Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing 100083, China
| | - Jun Sun
- College of Food Science and Nutritional Engineering, National Engineering Research Centre for Fruit and Vegetable Processing, Key Laboratory of Fruits and Vegetables Processing, Ministry of Agriculture; Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing 100083, China
| | - Hanxiong Liu
- School of Food Science and Technology, National Engineering Research Center of Seafood, Dalian Polytechnic University, Dalian 116034, China
| | - Aroosa Mushtaq
- College of Food Science and Nutritional Engineering, National Engineering Research Centre for Fruit and Vegetable Processing, Key Laboratory of Fruits and Vegetables Processing, Ministry of Agriculture; Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing 100083, China
| | - Zhoumei Huang
- College of Food Science and Nutritional Engineering, National Engineering Research Centre for Fruit and Vegetable Processing, Key Laboratory of Fruits and Vegetables Processing, Ministry of Agriculture; Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing 100083, China
| | - Daotong Li
- College of Food Science and Nutritional Engineering, National Engineering Research Centre for Fruit and Vegetable Processing, Key Laboratory of Fruits and Vegetables Processing, Ministry of Agriculture; Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing 100083, China
| | - Lujia Zhang
- College of Food Science and Nutritional Engineering, National Engineering Research Centre for Fruit and Vegetable Processing, Key Laboratory of Fruits and Vegetables Processing, Ministry of Agriculture; Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing 100083, China
| | - Fang Chen
- College of Food Science and Nutritional Engineering, National Engineering Research Centre for Fruit and Vegetable Processing, Key Laboratory of Fruits and Vegetables Processing, Ministry of Agriculture; Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing 100083, China
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Iloki Assanga SB, Lewis Luján LM, McCarty MF. Targeting beta-catenin signaling for prevention of colorectal cancer - Nutraceutical, drug, and dietary options. Eur J Pharmacol 2023; 956:175898. [PMID: 37481200 DOI: 10.1016/j.ejphar.2023.175898] [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: 03/11/2023] [Revised: 06/09/2023] [Accepted: 06/29/2023] [Indexed: 07/24/2023]
Abstract
Progressive up-regulation of β-catenin signaling is very common in the transformation of colorectal epithelium to colorectal cancer (CRC). Practical measures for opposing such signaling hence have potential for preventing or slowing such transformation. cAMP/PKA activity in colon epithelium, as stimulated by COX-2-generated prostaglandins and β2-adrenergic signaling, boosts β-catenin activity, whereas cGMP/PKG signaling has the opposite effect. Bacterial generation of short-chain fatty acids (as supported by unrefined high-carbohydrate diets, berberine, and probiotics), dietary calcium, daily aspirin, antioxidants opposing cox-2 induction, and nicotine avoidance, can suppress cAMP production in colonic epithelium, whereas cGMP can be boosted via linaclotides, PDE5 inhibitors such as sildenafil or icariin, and likely high-dose biotin. Selective activation of estrogen receptor-β by soy isoflavones, support of adequate vitamin D receptor activity with UV exposure or supplemental vitamin D, and inhibition of CK2 activity with flavanols such as quercetin, can also oppose β-catenin signaling in colorectal epithelium. Secondary bile acids, the colonic production of which can be diminished by low-fat diets and berberine, can up-regulate β-catenin activity by down-regulating farnesoid X receptor expression. Stimulation of PI3K/Akt via insulin, IGF-I, TLR4, and EGFR receptors boosts β-catenin levels via inhibition of glycogen synthase-3β; plant-based diets can down-regulate insulin and IGF-I levels, exercise training and leanness can keep insulin low, anthocyanins and their key metabolite ferulic acid have potential for opposing TLR4 signaling, and silibinin is a direct antagonist for EGFR. Partially hydrolyzed phytate can oppose growth factor-mediated down-regulation of β-catenin by inhibiting Akt activation. Multifactorial strategies for safely opposing β-catenin signaling can be complemented with measures that diminish colonic mutagenesis and DNA hypomethylation - such as avoidance of heme-rich meat and charred or processed meats, consumption of phase II-inductive foods and nutraceuticals (e.g., Crucifera), and assurance of adequate folate status.
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Affiliation(s)
- Simon Bernard Iloki Assanga
- Departamento de Ciencias Químico Biológicas, Universidad de Sonora, Blvd Luis Encinas y Rosales S/N Col. Centro, Hermosillo, Sonora, C.P. 83000, Mexico.
| | - Lidianys María Lewis Luján
- Technological Institute of Hermosillo (ITH), Ave. Tecnológico y Periférico Poniente S/N, Col. Sahuaro, Hermosillo, Sonora, C.P. 83170, México.
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Wei J, Li Y, Ye Z, Li Y, Zhou Z. Citrus Carotenoid Extracts Exert Anticancer Effects through Anti-Proliferation, Oxidative Stress, and Mitochondrial-Dependent Apoptosis in MCF-7 Cells. Foods 2023; 12:3469. [PMID: 37761178 PMCID: PMC10529845 DOI: 10.3390/foods12183469] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Revised: 09/14/2023] [Accepted: 09/15/2023] [Indexed: 09/29/2023] Open
Abstract
Citrus is a globally popular fruit crop that contains bioactive compounds with numerous health benefits. Carotenoids are one of the main bioactive compounds present in citrus pulp. They possess exceptional antioxidant and anticancer properties, making them potentially effective in the prevention and treatment of breast cancer. Different citrus species, identified as ZMPG, DFGJ, NFMJ, XY, and ZHQC, were studied for their antioxidant activity and anticancer activity. XY had the highest total carotenoid content (75.30 µg/g FW), and ZHQC (ZH) had the lowest carotenoid content (19.74 µg/g FW). The composition of NFMJ, ZMPG, and DFHJ consisted of the most abundant number of carotenoids, while XY only had three types. The antioxidant capacity of the carotenoid extracts was evaluated, and ZH and DFHJ were identified as good sources of antioxidants. XY and ZH significantly inhibited cell proliferation, migration, and arresting cells during the G0/G1 phase. XY and ZH enhanced the accumulation of reactive oxygen species (ROS); reduced mitochondrial membrane potential (MMP); reduced the activities of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), and peroxidase (POD); decreased glutathione (GSH) levels; and increased the malonaldehyde (MDA) content. Apoptosis occurred through the mitochondrial-mediated pathway through the up-regulation of BAX, caspase-3, and caspase-9 and the down-regulation of Bcl-2. In this study, the carotenoid-rich extracts of citrus pulp were found to induce oxidative stress through their pro-oxidant potential and regulate cell apoptosis in MCF-7 cancer cells. These results indicate that citrus carotenoids act as pro-oxidants and have the potential to be utilized for the development of anti-breast cancer products.
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Affiliation(s)
- Juanjuan Wei
- Key Laboratory of Agricultural Biosafety and Green Production of Upper Yangtze River (Ministry of Education), College of Horticulture and Landscape Architecture, Southwest University, Beibei District, Chongqing 400715, China; (J.W.); (Y.L.); (Z.Y.)
| | - Yurong Li
- Key Laboratory of Agricultural Biosafety and Green Production of Upper Yangtze River (Ministry of Education), College of Horticulture and Landscape Architecture, Southwest University, Beibei District, Chongqing 400715, China; (J.W.); (Y.L.); (Z.Y.)
| | - Zimao Ye
- Key Laboratory of Agricultural Biosafety and Green Production of Upper Yangtze River (Ministry of Education), College of Horticulture and Landscape Architecture, Southwest University, Beibei District, Chongqing 400715, China; (J.W.); (Y.L.); (Z.Y.)
| | - Yi Li
- Zhejiang Citrus Research Institute, Taizhou 318020, China;
| | - Zhiqin Zhou
- Key Laboratory of Agricultural Biosafety and Green Production of Upper Yangtze River (Ministry of Education), College of Horticulture and Landscape Architecture, Southwest University, Beibei District, Chongqing 400715, China; (J.W.); (Y.L.); (Z.Y.)
- The Southwest Institute of Fruits Nutrition, Banan District, Chongqing 400054, China
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Bocian-Jastrzębska A, Malczewska-Herman A, Kos-Kudła B. Role of Leptin and Adiponectin in Carcinogenesis. Cancers (Basel) 2023; 15:4250. [PMID: 37686525 PMCID: PMC10486522 DOI: 10.3390/cancers15174250] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 08/18/2023] [Accepted: 08/21/2023] [Indexed: 09/10/2023] Open
Abstract
Hormones produced by adipocytes, leptin and adiponectin, are associated with the process of carcinogenesis. Both of these adipokines have well-proven oncologic potential and can affect many aspects of tumorigenesis, from initiation and primary tumor growth to metastatic progression. Involvement in the formation of cancer includes interactions with the tumor microenvironment and its components, such as tumor-associated macrophages, cancer-associated fibroblasts, extracellular matrix and matrix metalloproteinases. Furthermore, these adipokines participate in the epithelial-mesenchymal transition and connect to angiogenesis, which is critical for cancer invasiveness and cancer cell migration. In addition, an enormous amount of evidence has demonstrated that altered concentrations of these adipocyte-derived hormones and the expression of their receptors in tumors are associated with poor prognosis in various types of cancer. Therefore, leptin and adiponectin dysfunction play a prominent role in cancer and impact tumor invasion and metastasis in different ways. This review clearly and comprehensively summarizes the recent findings and presents the role of leptin and adiponectin in cancer initiation, promotion and progression, focusing on associations with the tumor microenvironment and its components as well as roles in the epithelial-mesenchymal transition and angiogenesis.
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Affiliation(s)
- Agnes Bocian-Jastrzębska
- Department of Endocrinology and Neuroendocrine Tumors, Department of Pathophysiology and Endocrinogy, Medical University of Silesia, 40-514 Katowice, Poland; (A.M.-H.); (B.K.-K.)
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Lozano-Casabianca GA, Arango-Varela SS, Maldonado-Celis ME. Induction of Apoptosis and Decrease of Autophagy in Colon Cancer Cells by an Extract of Lyophilized Mango Pulp. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2023; 20:4165. [PMID: 36901174 PMCID: PMC10002435 DOI: 10.3390/ijerph20054165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/29/2023] [Revised: 02/19/2023] [Accepted: 02/23/2023] [Indexed: 06/18/2023]
Abstract
Previous studies have indicated that mango fruit has a chemopreventive capacity against colorectal cancer cells. The objective of this research was to evaluate the effect of an aqueous extract of lyophilized mango pulp (LMPE) on colon adenocarcinoma cells (SW480) and their metastatic derivatives (SW620) death and cellular invasion. DNA fragmentation was assessed by TUNEL assay; autophagy and expression of DR4 and Bcl-2 by flow cytometry; the expression of 35 apoptosis-related proteins and of matrix metalloproteinases 7 and 9 by immunodetection; and the invasive capacity of the cells by Boyden chamber. The results showed that LMPE at 30 mg/mL and 48 h of exposure results in DNA fragmentation and apoptosis in SW480 (p < 0.001) and SW620 (p < 0.01) cells. Additionally, LMPE decreased autophagy in the SW480 and SW620 cell lines (p < 0.001), which could sensitize them to the DNA damage generated by LMPE. The LMPE did not modulate the expression of matrix metalloproteinases 7 and 9, nor did it affect cellular invasion processes in the SW480 and SW620 cell lines. In conclusion, LMPE induces apoptosis and decreases autophagy in SW480 and SW620 cells.
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Affiliation(s)
| | - Sandra Sulay Arango-Varela
- Facultad de Ciencias Exactas y Aplicadas, Instituto Tecnológico Metropolitano (ITM), Institución Universitaria, Medellín 050034, Colombia
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Lycopene protects against Bisphenol A induced toxicity on the submandibular salivary glands via the upregulation of PPAR-γ and modulation of Wnt/β-catenin signaling. Int Immunopharmacol 2022; 112:109293. [DOI: 10.1016/j.intimp.2022.109293] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2022] [Revised: 09/20/2022] [Accepted: 09/25/2022] [Indexed: 11/13/2022]
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Luo M, Mai M, Song W, Yuan Q, Feng X, Xia E, Guo H. The Antiaging Activities of Phytochemicals in Dark-Colored Plant Foods: Involvement of the Autophagy- and Apoptosis-Associated Pathways. Int J Mol Sci 2022; 23:ijms231911038. [PMID: 36232338 PMCID: PMC9569742 DOI: 10.3390/ijms231911038] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Revised: 09/07/2022] [Accepted: 09/13/2022] [Indexed: 11/23/2022] Open
Abstract
In the last two decades, human life expectancy has increased by about 10 years, but this has not been accompanied by a corresponding increase in healthy lifespan. Aging is associated with a wide range of human disorders, including cancer, diabetes, and cardiovascular and neurodegenerative diseases. Delaying the aging of organs or tissues and improving the physiological functions of the elderly can reduce the risk of aging-related diseases. Autophagy and apoptosis are crucial mechanisms for cell survival and tissue homeostasis, and may also be primary aging-regulatory pathways. Recent epidemiological studies have shown that eating more colorful plant foods could increase life expectancy. Several representative phytochemicals in dark-colored plant foods such as quercetin, catechin, curcumin, anthocyanins, and lycopene have apparent antiaging potential. Nevertheless, the antiaging signaling pathways of the phytochemicals from dark-colored plant foods remain elusive. In the present review, we summarized autophagy- and apoptosis-associated targeting pathways of those phytochemicals and discussed the core targets involved in the antiaging effects. Further clinical evaluation and exploitation of phytochemicals as antiaging agents are needed to develop novel antiaging therapeutics for preventing age-related diseases and improving a healthy lifespan.
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Affiliation(s)
- Mengliu Luo
- Department of Nutrition, School of Public Health, Guangdong Medical University, Dongguan 523808, China
| | - Meiqing Mai
- Department of Nutrition, School of Public Health, Guangdong Medical University, Dongguan 523808, China
| | - Wanhan Song
- Department of Nutrition, School of Public Health, Guangdong Medical University, Dongguan 523808, China
| | - Qianhua Yuan
- Department of Nutrition, School of Public Health, Guangdong Medical University, Dongguan 523808, China
| | - Xiaoling Feng
- Department of Nutrition, School of Public Health, Guangdong Medical University, Dongguan 523808, China
| | - Enqin Xia
- Department of Nutrition, School of Public Health, Guangdong Medical University, Dongguan 523808, China
| | - Honghui Guo
- Department of Nutrition, School of Public Health, Guangdong Medical University, Dongguan 523808, China
- Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan 523808, China
- Correspondence: ; Tel.: +86-769-2289-6576
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Islam F, Mitra S, Emran TB, Khan Z, Nath N, Das R, Sharma R, Awadh AAA, Park MN, Kim B. Natural Small Molecules in Gastrointestinal Tract and Associated Cancers: Molecular Insights and Targeted Therapies. MOLECULES (BASEL, SWITZERLAND) 2022; 27:molecules27175686. [PMID: 36080453 PMCID: PMC9457641 DOI: 10.3390/molecules27175686] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/24/2022] [Revised: 08/24/2022] [Accepted: 08/29/2022] [Indexed: 12/22/2022]
Abstract
Gastric cancer is one of the most common cancers of the gastrointestinal tract. Although surgery is the primary treatment, serious maladies that dissipate to other parts of the body may require chemotherapy. As there is no effective procedure to treat stomach cancer, natural small molecules are a current focus of research interest for the development of better therapeutics. Chemotherapy is usually used as a last resort for people with advanced stomach cancer. Anti-colon cancer chemotherapy has become increasingly effective due to drug resistance and sensitivity across a wide spectrum of drugs. Naturally-occurring substances have been widely acknowledged as an important project for discovering innovative medications, and many therapeutic pharmaceuticals are made from natural small molecules. Although the beneficial effects of natural products are as yet unknown, emerging data suggest that several natural small molecules could suppress the progression of stomach cancer. Therefore, the underlying mechanism of natural small molecules for pathways that are directly involved in the pathogenesis of cancerous diseases is reviewed in this article. Chemotherapy and molecularly-targeted drugs can provide hope to colon cancer patients. New discoveries could help in the fight against cancer, and future stomach cancer therapies will probably include molecularly formulated drugs.
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Affiliation(s)
- Fahadul Islam
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh
| | - Saikat Mitra
- Department of Pharmacy, Faculty of Pharmacy, University of Dhaka, Dhaka 1000, Bangladesh
| | - Talha Bin Emran
- Department of Pharmacy, BGC Trust University Bangladesh, Chittagong 4381, Bangladesh
- Correspondence: (T.B.E.); (B.K.)
| | - Zidan Khan
- Department of Pharmacy, International Islamic University Chittagong, Chittagong 4318, Bangladesh
| | - Nikhil Nath
- Department of Pharmacy, International Islamic University Chittagong, Chittagong 4318, Bangladesh
| | - Rajib Das
- Department of Pharmacy, Faculty of Pharmacy, University of Dhaka, Dhaka 1000, Bangladesh
| | - Rohit Sharma
- Department of Rasa Shastra and Bhaishajya Kalpana, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, Uttar Pradesh, India
| | - Ahmed Abdullah Al Awadh
- Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Najran University, P.O. Box 1988, Najran 61441, Saudi Arabia
| | - Moon Nyeo Park
- Department of Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 05254, Korea
| | - Bonglee Kim
- Department of Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 05254, Korea
- Correspondence: (T.B.E.); (B.K.)
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12
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Alhoshani NM, Al-Johani NS, Alkeraishan N, Alarifi S, Alkahtani S. Effect of lycopene as an adjuvant therapy with 5-florouracil in human colon cancer. Saudi J Biol Sci 2022; 29:103392. [PMID: 35957702 PMCID: PMC9358465 DOI: 10.1016/j.sjbs.2022.103392] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2022] [Revised: 06/18/2022] [Accepted: 07/20/2022] [Indexed: 11/17/2022] Open
Abstract
Colon cancer (CC) is among the most frequent human cancers. Although, there is improvement in diagnostic techniques and existing treatment possibilities. Still, there is an unmet need for a novel treatment regimen that will improve the patient's quality of life. Here, the role of lycopene as an adjuvant therapy with 5-fluorouracil (5-FU) was explored in Caco2 colon cancer cells. Cells were exposed to a dose (3 µg/ml) of 5-FU and three doses (60, 90, 120 µg/ml) of lycopene either alone or as a mixture with 5-FU. Cytotoxicity, genotoxicity, oxidative stress, gene expression, and apoptotic parameters were investigated in this study. Findings showed that 5-FU or lycopene alone induced a dose-dependent increase in cytotoxicity which was slightly reduced in lycopene mixtures. Apoptotic assays showed that 5-FU induced a significant level of apoptosis but not necrosis. However, a lycopene mixture with 5-FU enhanced 5-FU triggered apoptosis and promoted necrosis. The mixtures were also shown to suppress mitochondrial membrane potential while gene expression analyses showed the induction of Bax expression upon exposure to mix 90 exhibited the highest Bax to Bcl-2 ratio and caspase 3 and 9 gene expression. Furthermore, the mixture treatment also inhibited cell migration in the wound healing assay compared to 5-FU alone. In conclusion, lycopene was found to sensitize Caco 2 cell lines to 5-FU treatment by inducing the expression of apoptotic genes. This, coupled with lycopene suppression of cytotoxicity and cell migration, indicates lycopene may be a promising candidate for adjuvant therapy involving 5-FU in CC.
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Affiliation(s)
- Norah M. Alhoshani
- Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
| | - Norah S. Al-Johani
- Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
| | - Nora Alkeraishan
- Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
| | - Saud Alarifi
- Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
| | - Saad Alkahtani
- Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
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13
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Mahmod AI, Haif SK, Kamal A, Al-Ataby IA, Talib WH. Chemoprevention effect of the Mediterranean diet on colorectal cancer: Current studies and future prospects. Front Nutr 2022; 9:924192. [PMID: 35990343 PMCID: PMC9386380 DOI: 10.3389/fnut.2022.924192] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Accepted: 07/18/2022] [Indexed: 12/11/2022] Open
Abstract
Colorectal cancer (CRC) is the third most common cancer and the second most deadly cancer worldwide. Nevertheless, more than 70% of CRC cases are resulted from sporadic tumorigenesis and are not inherited. Since adenoma-carcinoma development is a slow process and may take up to 20 years, diet-based chemoprevention could be an effective approach in sporadic CRC. The Mediterranean diet is an example of a healthy diet pattern that consists of a combination of nutraceuticals that prevent several chronic diseases and cancer. Many epidemiological studies have shown the correlation between adherence to the Mediterranean diet and low incidence of CRC. The goal of this review is to shed the light on the anti-inflammatory and anti-colorectal cancer potentials of the natural bioactive compounds derived from the main foods in the Mediterranean diet.
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Affiliation(s)
- Asma Ismail Mahmod
- Department of Clinical Pharmacy and Therapeutic, Applied Science Private University, Amman, Jordan
| | - Shatha Khaled Haif
- Department of Pharmacy, Princess Sarvath Community College, Amman, Jordan
| | - Ayah Kamal
- Department of Clinical Pharmacy and Therapeutic, Applied Science Private University, Amman, Jordan
| | - Israa A Al-Ataby
- Department of Clinical Pharmacy and Therapeutic, Applied Science Private University, Amman, Jordan
| | - Wamidh H Talib
- Department of Clinical Pharmacy and Therapeutic, Applied Science Private University, Amman, Jordan
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14
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Linderalactone Suppresses Pancreatic Cancer Development In Vitro and In Vivo via Negatively Regulating PI3K/AKT Signaling Pathway. JOURNAL OF ONCOLOGY 2022; 2022:8675096. [PMID: 35966890 PMCID: PMC9371883 DOI: 10.1155/2022/8675096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Revised: 03/02/2022] [Accepted: 06/30/2022] [Indexed: 11/18/2022]
Abstract
Linderalactone is one of the main extracts of Linderae Radix, which is widely used in traditional Chinese medicine. There have been few studies on the antitumor effect of linderalactone in the past. In this study, we explored the anti-pancreatic cancer activity of linderalactone in vitro and in vivo. The results showed that linderalactone inhibited the proliferation of pancreatic cancer cells in a time- and dose-dependent manner. Cell migration and invasion were significantly inhibited by linderalactone. The cell cycle was arrested in the G2/M phase, and the expression levels of cell cycle-associated proteins changed significantly with linderalactone treatment. In addition, linderalactone induced cell apoptosis and altered the expression of apoptotic markers, such as caspase 3 and PARP1. Mechanistically, linderalactone suppressed the PI3K/AKT signaling pathway by downregulating the phosphorylation of PI3K and AKT. The xenograft study results were consistent with the in vitro results, and there was no obvious chemical toxicity. Thus, our research demonstrated that linderalactone exhibits antitumor activity against pancreatic cancer and may be developed as a potential anti-pancreatic cancer agent in the future.
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15
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Starska-Kowarska K. Dietary Carotenoids in Head and Neck Cancer-Molecular and Clinical Implications. Nutrients 2022; 14:nu14030531. [PMID: 35276890 PMCID: PMC8838110 DOI: 10.3390/nu14030531] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Revised: 01/07/2022] [Accepted: 01/12/2022] [Indexed: 01/27/2023] Open
Abstract
Head and neck cancer (HNC) is one of the most common cancers in the world according to GLOBCAN. In 2018, it was reported that HNC accounts for approximately 3% of all human cancers (51,540 new cases) and is the cause of nearly 1.5% of all cancer deaths (10,030 deaths). Despite great advances in treatment, HNC is indicated as a leading cause of death worldwide. In addition to having a positive impact on general health, a diet rich in carotenoids can regulate stages in the course of carcinogenesis; indeed, strong epidemiological associations exist between dietary carotenoids and HNS, and it is presumed that diets with carotenoids can even reduce cancer risk. They have also been proposed as potential chemotherapeutic agents and substances used in chemoprevention of HNC. The present review discusses the links between dietary carotenoids and HNC. It examines the prospective anticancer effect of dietary carotenoids against intracellular cell signalling and mechanisms, oxidative stress regulation, as well as their impact on apoptosis, cell cycle progression, cell proliferation, angiogenesis, metastasis, and chemoprevention; it also provides an overview of the limited preclinical and clinical research published in this arena. Recent epidemiological, key opinion-forming systematic reviews, cross-sectional, longitudinal, prospective, and interventional studies based on in vitro and animal models of HNC also indicate that high carotenoid content obtained from daily supplementation has positive effects on the initiation, promotion, and progression of HNC. This article presents these results according to their increasing clinical credibility.
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Affiliation(s)
- Katarzyna Starska-Kowarska
- Department of Physiology, Pathophysiology and Clinical Immunology, Department of Clinical Physiology, Medical University of Lodz, Żeligowskiego 7/9, 90-752 Lodz, Poland; ; Tel.: +48-604-541-412
- Department of Otorhinolaryngology, EnelMed Center Expert, Lodz, Drewnowska 58, 91-001 Lodz, Poland
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16
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Kubczak M, Szustka A, Rogalińska M. Molecular Targets of Natural Compounds with Anti-Cancer Properties. Int J Mol Sci 2021; 22:ijms222413659. [PMID: 34948455 PMCID: PMC8708931 DOI: 10.3390/ijms222413659] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 12/13/2021] [Accepted: 12/14/2021] [Indexed: 12/13/2022] Open
Abstract
Cancer is the second leading cause of death in humans. Despite rapid developments in diagnostic methods and therapies, metastasis and resistance to administrated drugs are the main obstacles to successful treatment. Therefore, the main challenge should be the diagnosis and design of optimal therapeutic strategies for patients to increase their chances of responding positively to treatment and increase their life expectancy. In many types of cancer, a deregulation of multiple pathways has been found. This includes disturbances in cellular metabolism, cell cycle, apoptosis, angiogenesis, or epigenetic modifications. Additionally, signals received from the microenvironment may significantly contribute to cancer development. Chemical agents obtained from natural sources seem to be very attractive alternatives to synthetic compounds. They can exhibit similar anti-cancer potential, usually with reduced side effects. It was reported that natural compounds obtained from fruits and vegetables, e.g., polyphenols, flavonoids, stilbenes, carotenoids and acetogenins, might be effective against cancer cells in vitro and in vivo. Several published results indicate the activity of natural compounds on protein expression by its influence on transcription factors. They could also be involved in alterations in cellular response, cell signaling and epigenetic modifications. Such natural components could be used in our diet for anti-cancer protection. In this review, the activities of natural compounds, including anti-cancer properties, are described. The influence of natural agents on cancer cell metabolism, proliferation, signal transduction and epigenetic modifications is highlighted.
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Affiliation(s)
- Małgorzata Kubczak
- Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-237 Łódź, Poland;
- Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-237 Łódź, Poland;
| | - Aleksandra Szustka
- Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-237 Łódź, Poland;
| | - Małgorzata Rogalińska
- Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-237 Łódź, Poland;
- Correspondence:
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17
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Siraj MA, Islam MA, Al Fahad MA, Kheya HR, Xiao J, Simal-Gandara J. Cancer Chemopreventive Role of Dietary Terpenoids by Modulating Keap1-Nrf2-ARE Signaling System—A Comprehensive Update. APPLIED SCIENCES 2021; 11:10806. [DOI: 10.3390/app112210806] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
ROS, RNS, and carcinogenic metabolites generate excessive oxidative stress, which changes the basal cellular status and leads to epigenetic modification, genomic instability, and initiation of cancer. Epigenetic modification may inhibit tumor-suppressor genes and activate oncogenes, enabling cells to have cancer promoting properties. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that in humans is encoded by the NFE2L2 gene, and is activated in response to cellular stress. It can regulate redox homoeostasis by expressing several cytoprotective enzymes, including NADPH quinine oxidoreductase, heme oxygenase-1, UDP-glucuronosyltransferase, glutathione peroxidase, glutathione-S-transferase, etc. There is accumulating evidence supporting the idea that dietary nutraceuticals derived from commonly used fruits, vegetables, and spices have the ability to produce cancer chemopreventive activity by inducing Nrf2-mediated detoxifying enzymes. In this review, we discuss the importance of these nutraceuticals in cancer chemoprevention and summarize the role of dietary terpenoids in this respect. This approach was taken to accumulate the mechanistic function of these terpenoids to develop a comprehensive understanding of their direct and indirect roles in modulating the Keap1-Nrf2-ARE signaling system.
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Affiliation(s)
- Md Afjalus Siraj
- Department of Pharmaceutical Sciences, Daniel K. Inouye College of Pharmacy, University of Hawaii at Hilo, Hilo, HI 96720, USA
| | - Md. Arman Islam
- Pharmacy Discipline, Life Science School, Khulna University, Khulna 9208, Bangladesh
| | - Md. Abdullah Al Fahad
- Department of Regenerative Medicine, College of Medicine, Soonchunhyang University, Cheonan 31151, Korea
| | - Habiba Rahman Kheya
- Department of Sociology, Faculty of Social Sciences, University of Dhaka, Dhaka 1000, Bangladesh
| | - Jianbo Xiao
- Nutrition and Bromatology Group, Department of Analytical and Food Chemistry, Faculty of Food Science and Technology, University of Vigo—Ourense Campus, E32004 Ourense, Spain
| | - Jesus Simal-Gandara
- Nutrition and Bromatology Group, Department of Analytical and Food Chemistry, Faculty of Food Science and Technology, University of Vigo—Ourense Campus, E32004 Ourense, Spain
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18
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Song X, Luo Y, Ma L, Hu X, Simal-Gandara J, Wang LS, Bajpai VK, Xiao J, Chen F. Recent trends and advances in the epidemiology, synergism, and delivery system of lycopene as an anti-cancer agent. Semin Cancer Biol 2021; 73:331-346. [PMID: 33794344 DOI: 10.1016/j.semcancer.2021.03.028] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Revised: 03/20/2021] [Accepted: 03/22/2021] [Indexed: 02/07/2023]
Affiliation(s)
- Xunyu Song
- College of Food Science and Nutritional Engineering, National Engineering Research Centre for Fruit and Vegetable Processing, Key Laboratory of Fruits and Vegetables Processing, Ministry of Agriculture, Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing 100083, China
| | - Yinghua Luo
- College of Food Science and Nutritional Engineering, National Engineering Research Centre for Fruit and Vegetable Processing, Key Laboratory of Fruits and Vegetables Processing, Ministry of Agriculture, Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing 100083, China
| | - Lingjun Ma
- College of Food Science and Nutritional Engineering, National Engineering Research Centre for Fruit and Vegetable Processing, Key Laboratory of Fruits and Vegetables Processing, Ministry of Agriculture, Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing 100083, China
| | - Xiaosong Hu
- College of Food Science and Nutritional Engineering, National Engineering Research Centre for Fruit and Vegetable Processing, Key Laboratory of Fruits and Vegetables Processing, Ministry of Agriculture, Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing 100083, China
| | - Jesus Simal-Gandara
- Nutrition and Bromatology Group, Department of Analytical Chemistry and Food Science, Faculty of Food Science and Technology, University of Vigo - Ourense Campus, E-32004 Ourense, Spain
| | - Li-Shu Wang
- Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA
| | - Vivek K Bajpai
- Department of Energy and Materials Engineering, Dongguk University, 30 Pildong-ro 1-gil, Seoul 04620, Republic of Korea
| | - Jianbo Xiao
- Nutrition and Bromatology Group, Department of Analytical Chemistry and Food Science, Faculty of Food Science and Technology, University of Vigo - Ourense Campus, E-32004 Ourense, Spain.
| | - Fang Chen
- College of Food Science and Nutritional Engineering, National Engineering Research Centre for Fruit and Vegetable Processing, Key Laboratory of Fruits and Vegetables Processing, Ministry of Agriculture, Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing 100083, China.
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Puah BP, Jalil J, Attiq A, Kamisah Y. New Insights into Molecular Mechanism behind Anti-Cancer Activities of Lycopene. Molecules 2021; 26:molecules26133888. [PMID: 34202203 PMCID: PMC8270321 DOI: 10.3390/molecules26133888] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2021] [Revised: 06/05/2021] [Accepted: 06/17/2021] [Indexed: 12/15/2022] Open
Abstract
Lycopene is a well-known compound found commonly in tomatoes which brings wide range of health benefits against cardiovascular diseases and cancers. From an anti-cancer perspective, lycopene is often associated with reduced risk of prostate cancer and people often look for it as a dietary supplement which may help to prevent cancer. Previous scientific evidence exhibited that the anti-cancer activity of lycopene relies on its ability to suppress oncogene expressions and induce proapoptotic pathways. To further explore the real potential of lycopene in cancer prevention, this review discusses the new insights and perspectives on the anti-cancer activities of lycopene which could help to drive new direction for research. The relationship between inflammation and cancer is being highlighted, whereby lycopene suppresses cancer via resolution of inflammation are also discussed herein. The immune system was found to be a part of the anti-cancer system of lycopene as it modulates immune cells to suppress tumor growth and progression. Lycopene, which is under the family of carotenoids, was found to play special role in suppressing lung cancer.
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Affiliation(s)
- Boon-Peng Puah
- Drug and Herbal Research Centre, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, Malaysia;
| | - Juriyati Jalil
- Drug and Herbal Research Centre, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, Malaysia;
- Correspondence: ; Tel.: +603-9289-7533
| | - Ali Attiq
- Faculty of Pharmacy, MAHSA University, Bandar Saujana Putra, Jenjarom 42610, Malaysia;
| | - Yusof Kamisah
- Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Malaysia;
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Qi WJ, Sheng WS, Peng C, Xiaodong M, Yao TZ. Investigating into anti-cancer potential of lycopene: Molecular targets. Biomed Pharmacother 2021; 138:111546. [PMID: 34311540 DOI: 10.1016/j.biopha.2021.111546] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Revised: 03/17/2021] [Accepted: 03/23/2021] [Indexed: 01/06/2023] Open
Abstract
Lycopene, the main pigment of tomatoes, possess the strongest antioxidant activity among carotenoids. Lycopene has unique structure and chemical properties. We searched the literature, via PubMed, Embase, Web of Science and Google database so on to screen citations from inception to Oct 2020 for inclusion in this study. We found that as a common phytochemical, it did not attract much attention in the past few years. However, recent studies have indicated that, in addition to antioxidant activity and the second stage of detoxification, the anticancer of lycopene is also considered to be an important determinant of tumor development including the inhibition of cell proliferation, inhibition of cell cycle progression, induction of apoptosis, inhibition of cell invasion, angiogenesis and metastasis. The effect mechanisms of lycopene are related to the regulation of several signal transduction pathways, such as PI3K/Akt pathway, modulation of insulin-like growth factors system, the suppression of activity of sex steroid hormones, the modification of relevant gene expression, and the alteration of mitochondrial function. These novel findings have suggested that lycopene acts as a promising functional natural pigment, and may be associated with a decreased risk of different types of cancer. This review presents the latest knowledge with respect to its molecular mechanisms and its molecular targets of the inhibitory effects on carcinogenesis.
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Affiliation(s)
- Wang Jia Qi
- Department of Plastic and Reconstructive Surgery, The First Bethune Hospital of Jilin University, No. 71, Xin Min Street, Changchun 130021, Jilin, China
| | - Wang Shi Sheng
- College of Pharmaceutical Science and Technology, Dalian University of Technology, Dalian 116023, China
| | - Chu Peng
- Pharmacological Department, Dalian Medical University, Dalian 116044, Liaoning, China
| | - Ma Xiaodong
- Pharmacological Department, Dalian Medical University, Dalian 116044, Liaoning, China
| | - Tang Ze Yao
- Pharmacological Department, Dalian Medical University, Dalian 116044, Liaoning, China.
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21
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Shejawal KP, Randive DS, Bhinge SD, Bhutkar MA, Todkar SS, Mulla AS, Jadhav NR. Green synthesis of silver, iron and gold nanoparticles of lycopene extracted from tomato: their characterization and cytotoxicity against COLO320DM, HT29 and Hella cell. JOURNAL OF MATERIALS SCIENCE. MATERIALS IN MEDICINE 2021; 32:19. [PMID: 33576907 PMCID: PMC7880933 DOI: 10.1007/s10856-021-06489-8] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Accepted: 01/18/2021] [Indexed: 05/04/2023]
Abstract
Our study aimed at development of Silver, Iron and Gold nanoparticles of Lycopene isolated from tomato by using green synthesis technique and to evaluate its anticancer potential against colorectal and cervical cancer. Lycopene was extracted by benzene extraction method and the silver, iron and gold nanoparticles were developed by green synthesis method. 1% aqueous extract of isolated Lycopene was mixed with 1% solutions of AgNO3, FeCl3 and HAuCl4 solutions and incubated at ambient temperature for 3-4 h separately and observed for the color change which is an indicative of formation of the nanoparticles. The prepared nanoparticles were characterized by FTIR, SEM, XRD analysis and evaluated for their antimicrobial potential. The cytotoxicity studies were carried out by in vitro assay like MTT, SRB and Tryphan blue method against Colo 320 DM, HT 29, and Hella. SEM showed nanosized particles of 50-100 nm range, whereas no antimicrobial activity was exhibited by the prepared nanoparticles. In MTT assay the LyAgNP showed maximum 41.41 ± 0.4124% inhibition against COLO320DM, whereas LyGNP exhibited 41.47 ± 0.4469% inhibition against HT 29 and LyAgNP showed 40.9 ± 0.6908% inhibition against Hella cells. In SRB assay LyAgNP showed maximum 82.68 ± 1.1798% inhibition against COLO320DM, whereas LyGNP exhibited maximum 91.21 ± 0.2372% inhibition against HT29 and 87.98 ± 0.5878% inhibition against Hella cells. In tryphan blue assay against COLO320DM, HT29 and Hella cells, the maximum inhibition exhibited by the prepared nanoparticles were observed as LyGNP 83.45 ± 0.4694%, LyAgNP 88.05 ± 0.1870% and LyAgNP65.47 ± 0.4766%. We conclude that the developed nanoparticles of Lycopene exhibited potential anticancer activity against Colorectal and cervical cancer cell as compared with pure Lycopene.
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Affiliation(s)
- Kiran P Shejawal
- Department of Pharmaceutics Rajarambapu College of Pharmacy, Kasegaon, Walwa, Sangli, Maharashtra, 415404, India.
| | - Dheeraj S Randive
- Department of Pharmaceutics Rajarambapu College of Pharmacy, Kasegaon, Walwa, Sangli, Maharashtra, 415404, India
| | - Somnath D Bhinge
- Department of Pharmaceutical Chemistry Rajarambapu College of Pharmacy, Kasegaon, Walwa, Sangli, Maharashtra, 415404, India
| | - Mangesh A Bhutkar
- Department of Pharmaceutics Rajarambapu College of Pharmacy, Kasegaon, Walwa, Sangli, Maharashtra, 415404, India
| | - Sachin S Todkar
- Department of Pharmaceutical Chemistry Rajarambapu College of Pharmacy, Kasegaon, Walwa, Sangli, Maharashtra, 415404, India
| | - Anjum S Mulla
- Department of Pharmaceutics Rajarambapu College of Pharmacy, Kasegaon, Walwa, Sangli, Maharashtra, 415404, India
| | - Namdeo R Jadhav
- Department of Pharmaceutics Bharati vidyapeeth College of Pharmacy, Kolhapur, Maharashtra, 416013, India
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22
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Gao L, Gou N, Yao M, Amakye WK, Ren J. Food-derived natural compounds in the management of chronic diseases via Wnt signaling pathway. Crit Rev Food Sci Nutr 2021; 62:4769-4799. [PMID: 33554630 DOI: 10.1080/10408398.2021.1879001] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Wnt signaling pathway is an evolutionarily conserved pathway that control embryonic development, adult tissue homeostasis, and pathological processes of organisms throughout life. However, dysregulation of the Wnt signaling is associated with the occurrence of chronic diseases. In comparison with the application of chemical drugs as traditional treatment for chronic diseases, dietary agents have unique advantages, such as less side effects, multiple targets, convenience in accessibility and higher acceptability in long-term intervention. In this review, we summarized current progress in manipulating the Wnt signaling using food components and its benefits in managing chronic diseases. The underlying mechanisms of bioactive food components in the management of the disease progression via the Wnt signaling was illustrated. Then, the review focused on the function of dietary pattern (which might act via combination of foods with multiple nutrients or food ingredients) on targeting Wnt signaling at multiple level. The potential caveats and challenges in developing new strategy via modulating Wnt-associated diseases with food-based agents and appropriate dietary pattern are also discussed in detail. This review shed light on the understanding of the regulatory effect of food bioactive components on chronic diseases management through the Wnt signaling, which can be expanded to other specific signaling pathway associated with disease.
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Affiliation(s)
- Li Gao
- School of Food Science and Engineering, South China University of Technology, Guangzhou, China
| | - Na Gou
- School of Food Science and Engineering, South China University of Technology, Guangzhou, China
| | - Maojin Yao
- Guangzhou Institute of Respiratory Disease & China State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - William Kwame Amakye
- School of Food Science and Engineering, South China University of Technology, Guangzhou, China
| | - Jiaoyan Ren
- School of Food Science and Engineering, South China University of Technology, Guangzhou, China.,Research Institute for Food Nutrition and Human Health, Guangzhou, China
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Chang ML, Yang Z, Yang SS. Roles of Adipokines in Digestive Diseases: Markers of Inflammation, Metabolic Alteration and Disease Progression. Int J Mol Sci 2020; 21:E8308. [PMID: 33167521 PMCID: PMC7663948 DOI: 10.3390/ijms21218308] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 10/30/2020] [Accepted: 11/01/2020] [Indexed: 12/13/2022] Open
Abstract
Adipose tissue is a highly dynamic endocrine tissue and constitutes a central node in the interorgan crosstalk network through adipokines, which cause pleiotropic effects, including the modulation of angiogenesis, metabolism, and inflammation. Specifically, digestive cancers grow anatomically near adipose tissue. During their interaction with cancer cells, adipocytes are reprogrammed into cancer-associated adipocytes and secrete adipokines to affect tumor cells. Moreover, the liver is the central metabolic hub. Adipose tissue and the liver cooperatively regulate whole-body energy homeostasis via adipokines. Obesity, the excessive accumulation of adipose tissue due to hyperplasia and hypertrophy, is currently considered a global epidemic and is related to low-grade systemic inflammation characterized by altered adipokine regulation. Obesity-related digestive diseases, including gastroesophageal reflux disease, Barrett's esophagus, esophageal cancer, colon polyps and cancer, non-alcoholic fatty liver disease, viral hepatitis-related diseases, cholelithiasis, gallbladder cancer, cholangiocarcinoma, pancreatic cancer, and diabetes, might cause specific alterations in adipokine profiles. These patterns and associated bases potentially contribute to the identification of prognostic biomarkers and therapeutic approaches for the associated digestive diseases. This review highlights important findings about altered adipokine profiles relevant to digestive diseases, including hepatic, pancreatic, gastrointestinal, and biliary tract diseases, with a perspective on clinical implications and mechanistic explorations.
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Affiliation(s)
- Ming-Ling Chang
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan 33305, Taiwan
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan
| | - Zinger Yang
- Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA;
| | - Sien-Sing Yang
- Liver Center, Cathay General Hospital Medical Center, Taipei 10630, Taiwan;
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Hong Z, Xiao N, Li L, Xie X. Investigation of nanoemulsion interfacial properties: A mesoscopic simulation. J FOOD ENG 2020. [DOI: 10.1016/j.jfoodeng.2019.109877] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
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Mirahmadi M, Azimi-Hashemi S, Saburi E, Kamali H, Pishbin M, Hadizadeh F. Potential inhibitory effect of lycopene on prostate cancer. Biomed Pharmacother 2020; 129:110459. [PMID: 32768949 DOI: 10.1016/j.biopha.2020.110459] [Citation(s) in RCA: 72] [Impact Index Per Article: 14.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2020] [Revised: 06/13/2020] [Accepted: 06/23/2020] [Indexed: 12/12/2022] Open
Abstract
Studying prostate cancer is important due to its high annual incidences and mortality rates in the world. Although prostate cancer mortality rates are reduced using new therapy, complicated routes and side effects of these current drugs require a daily available treatment for prevention. Lycopene is a natural, prominent, and effective product which has a high value in diet. The anti-cancer effect, non-toxicity, safety and preventive or therapeutic roles of lycopene have been investigated in several studies. In the current review, we have collected information about the anti-cancer, anti-progressive and apoptotic effects of lycopene on prostate cancer. This article is a summary of the most important original and review articles on lycopene and its anticancer effects that are systematically categorized and presents information about the molecular structure, different sources, biological functions, and its in-vivo and in-vitro effects of lycopene on variety of cancerous and normal cells. The clinical studies provide a clear image for continuous use of this adjunctive dietary for different type of cancers, especially prostate cancer in men. In addition, this article discusses the various molecular pathways activated by lycopene that eventually prevent or suppress cancer. Lycopene has been found to effectively suppress the progression and proliferation, arrest in-cell cycle, and induce apoptosis of prostate cancer cells in both in-vivo and in-vitro conditions. Additionally, lycopene showed that it could modulate the signaling pathways and their protein for the treatment or prevention of prostate cancer.
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Affiliation(s)
- Mahdi Mirahmadi
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Cancer Research, Nastran Center for Cancer Prevention (NCCP), Mashhad, Iran
| | - Shayan Azimi-Hashemi
- Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Ehsan Saburi
- Medical Genetics and Molecular Medicine Department, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hossein Kamali
- Department of Pharmaceutics, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mandana Pishbin
- Iranian Blood Transfusion Organization, Khorasan Razavi Center, Mashhad, Iran
| | - Farzin Hadizadeh
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
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Saini RK, Keum YS, Daglia M, Rengasamy KR. Dietary carotenoids in cancer chemoprevention and chemotherapy: A review of emerging evidence. Pharmacol Res 2020; 157:104830. [PMID: 32344050 DOI: 10.1016/j.phrs.2020.104830] [Citation(s) in RCA: 77] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Revised: 04/10/2020] [Accepted: 04/10/2020] [Indexed: 12/20/2022]
Abstract
In recent years, natural products have reemerged as biotherapeutic options, with several dietary carotenoids, viz. astaxanthin, fucoxanthin, siphonaxanthin, β-cryptoxanthin, α-carotene, β-carotene, and lycopene, developing as potential candidates for chemoprevention and chemotherapeutics of breast, colorectal, lung, and prostate cancers. The potent cytotoxic and antiproliferative effects of carotenoids against various cancer cells are mediated by a wide range of molecular mechanisms modulating oxidative stress and redox balance, mitogen-activated protein kinases (MAPK) and other cellular signaling proteins, transcription factors, caspase cascade pathways of apoptosis, cell cycle progression and proliferation, angiogenesis, metastasis, gap junction intercellular communication (GJIC), and multidrug resistance (MDR). This review discusses recent evidence demonstrating the crucial roles of carotenoids in these cellular and molecular events of cancer cell cytotoxicity. In addition, recent case-control and cohort studies are discussed to support the potential role of carotenoids in cancer prevention and therapy.
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Affiliation(s)
- Ramesh Kumar Saini
- Department of Bioresources and Food Science, Konkuk University, Seoul 143-701, Republic of Korea; Institute of Natural Science and Agriculture, Konkuk University, Seoul 143-701, Republic of Korea; Department of Crop Science, Konkuk University, Seoul 143-701, Republic of Korea
| | - Young-Soo Keum
- Department of Crop Science, Konkuk University, Seoul 143-701, Republic of Korea
| | - Maria Daglia
- Department of Drug Sciences, Medicinal Chemistry and Pharmaceutical Technology Section, Pavia University, Viale Taramelli 12, Pavia, 27100, Italy
| | - Kannan Rr Rengasamy
- Department of Bioresources and Food Science, Konkuk University, Seoul 143-701, Republic of Korea.
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Zhang T, Pan D, Yang Y, Jiang X, Zhang J, Zeng X, Wu Z, Sun Y, Guo Y. Effect of Lactobacillus acidophilus CICC 6074 S-Layer Protein on Colon Cancer HT-29 Cell Proliferation and Apoptosis. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2020; 68:2639-2647. [PMID: 32000489 DOI: 10.1021/acs.jafc.9b06909] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/26/2023]
Abstract
The objective of this research was to investigate the effects of Lactobacillus acidophilus CICC 6074 S-layer protein on the viability, adhesion, cell cycle, and apoptosis of human colon cancer HT-29 cells and to explore their molecular mechanism of tumor suppression. The S-layer protein at doses of 0, 25, 50, and 100 mg/L significantly suppressed the proliferation of HT-29 cells. The S-layer protein exerts its cytotoxic activities against colon cancer HT-29 cells by arresting the cell cycle in the G1 phase through upregulating the expression of p53, p21, and p16 and downregulating the expression of CDK1 (cyclin-dependent kinases) and cyclin B. Morphological changes were further observed by transmission electron microscopy, and the cells treated with the S-layer protein showed obvious characteristic changes of apoptosis including chromatin condensation, nuclear fragmentation, vacuoles, and so on. Furthermore, our mechanism studies indicated that the S-layer protein may induce HT-29 cell apoptosis through the death receptor apoptotic pathway and mitochondrial pathway and impede cell invasion by inhibiting the synthesis of the PI3K/AKT pathway and FasL. These results demonstrated that the L. acidophilus CICC 6074 S-layer protein may be a potential anticarcinogenic agent.
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Affiliation(s)
- Tao Zhang
- Department of Food Science and Technology, School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing, Jiangsu 210023, P. R. China
| | - Daodong Pan
- College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo, Zhejiang 315211, P. R. China
| | - Yujie Yang
- Department of Food Science and Technology, School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing, Jiangsu 210023, P. R. China
| | - Xiaoxiao Jiang
- Department of Food Science and Technology, School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing, Jiangsu 210023, P. R. China
| | - Jiaxin Zhang
- Department of Food Science and Technology, School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing, Jiangsu 210023, P. R. China
| | - Xiaoqun Zeng
- College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo, Zhejiang 315211, P. R. China
| | - Zhen Wu
- College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo, Zhejiang 315211, P. R. China
| | - Yangying Sun
- College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo, Zhejiang 315211, P. R. China
| | - Yuxing Guo
- Department of Food Science and Technology, School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing, Jiangsu 210023, P. R. China
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Saini RK, Rengasamy KRR, Mahomoodally FM, Keum YS. Protective effects of lycopene in cancer, cardiovascular, and neurodegenerative diseases: An update on epidemiological and mechanistic perspectives. Pharmacol Res 2020; 155:104730. [PMID: 32126272 DOI: 10.1016/j.phrs.2020.104730] [Citation(s) in RCA: 98] [Impact Index Per Article: 19.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2019] [Revised: 02/26/2020] [Accepted: 02/26/2020] [Indexed: 12/22/2022]
Abstract
Recent mechanistic and epidemiological studies have provided insights into health benefits of dietary lycopene to decrease the risk and complications associated with several chronic diseases such as cardiovascular diseases (CVD), obesity, type 2 diabetes, cancer, and neurodegenerative disorders. These chronic diseases are primarily associated with oxidative stress-induced systemic and low-grade chronic inflammation. Owing to its potent antioxidant properties, lycopene can potentially alleviate enhanced levels of proinflammatory mediators (e.g., proinflammatory cytokines IL-8, -6, and -1, and oxidized phospholipids) and prevent NF-κB activation by modulating oxidative stress. Moreover, lycopene serves as a precursor for various oxidative cleavage products and metabolites including Apo-8'-, apo-10'-, and apo-12'-lycopenals that can interact with multiple transcription factors (e.g., Nrf2, RARs, RXRs, and PPARs) to overexpress antioxidant and cytoprotective Phase II enzymes and other growth-stimulating proteins (e.g., brain-derived neurotrophic factor (BDNF) for enhanced neuroprotection. These events altogether can protect the body from chronic inflammatory disorders. In the present review, the latest mechanistic development from cell and animal models and results of case-control, cohort, and randomized trials are discussed to support the protective part of lycopene in cancer, CVD, and neurodegenerative disorders. This review focuses on cellular and molecular events involved in protective effects of lycopene. Although molecular and cellular mechanisms involved in health-promoting activities of lycopene have been reported, no detailed mechanistic studies have been published. Hence, future studies should be conducted to elucidate the mechanistic role(s) of lycopene-derived oxidation products in modulating cellular signaling.
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Affiliation(s)
- Ramesh Kumar Saini
- Department of Bioresources and Food Science, Konkuk University, Seoul 143-701, Republic of Korea; Institute of Natural Science and Agriculture, Konkuk University, Seoul 143-701, Republic of Korea; Department of Crop Science, Konkuk University, Seoul 143-701, Republic of Korea
| | - Kannan R R Rengasamy
- Department of Bioresources and Food Science, Konkuk University, Seoul 143-701, Republic of Korea.
| | - Fawzi M Mahomoodally
- Institute of Research and Development, Duy Tan University, Da Nang 550000, Viet Nam; Department of Health Sciences, Faculty of Science, University of Mauritius, Réduit, Mauritius
| | - Young-Soo Keum
- Department of Crop Science, Konkuk University, Seoul 143-701, Republic of Korea
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Phytochemicals and Gastrointestinal Cancer: Cellular Mechanisms and Effects to Change Cancer Progression. Biomolecules 2020; 10:biom10010105. [PMID: 31936288 PMCID: PMC7022462 DOI: 10.3390/biom10010105] [Citation(s) in RCA: 83] [Impact Index Per Article: 16.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2019] [Revised: 12/21/2019] [Accepted: 12/23/2019] [Indexed: 02/07/2023] Open
Abstract
Gastrointestinal (GI) cancer is a prevailing global health disease with a high incidence rate which varies by region. It is a huge economic burden on health care providers. GI cancer affects different organs in the body such as the gastric organs, colon, esophagus, intestine, and pancreas. Internal and external factors like smoking, obesity, urbanization, genetic mutations, and prevalence of Helicobacter pylori and Hepatitis B and Hepatitis C viral infections could increase the risk of GI cancer. Phytochemicals are non-nutritive bioactive secondary compounds abundantly found in fruits, grains, and vegetables. Consumption of phytochemicals may protect against chronic diseases like cardiovascular disease, neurodegenerative disease, and cancer. Multiple studies have assessed the chemoprotective effect of selected phytochemicals in GI cancer, offering support to their potential towards reducing the pathogenesis of the disease. The aim of this review was to summarize the current knowledge addressing the anti-cancerous effects of selected dietary phytochemicals on GI cancer and their molecular activities on selected mechanisms, i.e., nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), detoxification enzymes, adenosine monophosphate activated protein kinase (AMPK), wingless-related integration site/β-catenin (wingless-related integration site (Wnt) β-catenin, cell apoptosis, phosphoinositide 3-kinases (PI3K)/ protein kinase B AKT/ mammalian target of rapamycin (mTOR), and mitogen-activated protein kinase (MAPK). In this review phytochemicals were classified into four main categories: (i) carotenoids, including lutein, lycopene, and β-carotene; (ii) proanthocyanidins, including quercetin and ellagic acid; (iii) organosulfur compounds, including allicin, allyl propyl disulphide, asparagusic acid, and sulforaphane; and (iv) other phytochemicals including pectin, curcumins, p-coumaric acid and ferulic acid. Overall, phytochemicals improve cancer prognosis through the downregulation of β-catenin phosphorylation, therefore enhancing apoptosis, and upregulation of the AMPK pathway, which supports cellular homeostasis. Nevertheless, more studies are needed to provide a better understanding of the mechanism of cancer treatment using phytochemicals and possible side effects associated with this approach.
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Maruca A, Catalano R, Bagetta D, Mesiti F, Ambrosio FA, Romeo I, Moraca F, Rocca R, Ortuso F, Artese A, Costa G, Alcaro S, Lupia A. The Mediterranean Diet as source of bioactive compounds with multi-targeting anti-cancer profile. Eur J Med Chem 2019; 181:111579. [PMID: 31398616 DOI: 10.1016/j.ejmech.2019.111579] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2019] [Revised: 07/29/2019] [Accepted: 07/30/2019] [Indexed: 12/20/2022]
Abstract
Many bioactive agents have been extracted from plants or belong to functional foods and have been considered in the treatment of serious and multifactorial diseases, such as cancer. In particular, this review is focused on the anti-cancer properties owned by several natural products typically from the Mediterranean area. In some regions of the South of Italy, a lower cancer incidence has been observed. There is increasing evidence that adherence to a Mediterranean dietary pattern correlates with reduced risk of several cancer types. This could be mainly attributed to the typical lifestyle aspects of the Mediterranean diet, such as high consumption of fruit and vegetables. In this review, the main natural products of the Mediterranean area are discussed, with particular attention on their anti-cancer properties endowed with multi-target profiles.
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Affiliation(s)
- Annalisa Maruca
- Dipartimento di Scienze della Salute, Università "Magna Græcia", Campus Salvatore Venuta, Viale Europa, 88100, Catanzaro, Italy; Net4Science srl, Università "Magna Græcia", Campus Salvatore Venuta, Viale Europa, 88100, Catanzaro, Italy
| | - Raffaella Catalano
- Dipartimento di Scienze della Salute, Università "Magna Græcia", Campus Salvatore Venuta, Viale Europa, 88100, Catanzaro, Italy; Net4Science srl, Università "Magna Græcia", Campus Salvatore Venuta, Viale Europa, 88100, Catanzaro, Italy
| | - Donatella Bagetta
- Dipartimento di Scienze della Salute, Università "Magna Græcia", Campus Salvatore Venuta, Viale Europa, 88100, Catanzaro, Italy; Net4Science srl, Università "Magna Græcia", Campus Salvatore Venuta, Viale Europa, 88100, Catanzaro, Italy
| | - Francesco Mesiti
- Dipartimento di Scienze della Salute, Università "Magna Græcia", Campus Salvatore Venuta, Viale Europa, 88100, Catanzaro, Italy; Net4Science srl, Università "Magna Græcia", Campus Salvatore Venuta, Viale Europa, 88100, Catanzaro, Italy
| | - Francesca Alessandra Ambrosio
- Dipartimento di Scienze della Salute, Università "Magna Græcia", Campus Salvatore Venuta, Viale Europa, 88100, Catanzaro, Italy
| | - Isabella Romeo
- Net4Science srl, Università "Magna Græcia", Campus Salvatore Venuta, Viale Europa, 88100, Catanzaro, Italy; Department of Chemistry and Chemical Technology, University of Calabria, Via Pietro Bucci, 87036, Arcavacata di Rende, Cosenza, Italy
| | - Federica Moraca
- Net4Science srl, Università "Magna Græcia", Campus Salvatore Venuta, Viale Europa, 88100, Catanzaro, Italy; Department of Pharmacy, University of Naples "Federico II", Via D. Montesano, 49, 80131, Naples, Italy
| | - Roberta Rocca
- Net4Science srl, Università "Magna Græcia", Campus Salvatore Venuta, Viale Europa, 88100, Catanzaro, Italy; Department of Experimental and Clinical Medicine "Magna Græcia" University, Campus Salvatore Venuta, Viale Europa, 88100, Catanzaro, Italy.
| | - Francesco Ortuso
- Dipartimento di Scienze della Salute, Università "Magna Græcia", Campus Salvatore Venuta, Viale Europa, 88100, Catanzaro, Italy; Net4Science srl, Università "Magna Græcia", Campus Salvatore Venuta, Viale Europa, 88100, Catanzaro, Italy
| | - Anna Artese
- Dipartimento di Scienze della Salute, Università "Magna Græcia", Campus Salvatore Venuta, Viale Europa, 88100, Catanzaro, Italy; Net4Science srl, Università "Magna Græcia", Campus Salvatore Venuta, Viale Europa, 88100, Catanzaro, Italy
| | - Giosuè Costa
- Dipartimento di Scienze della Salute, Università "Magna Græcia", Campus Salvatore Venuta, Viale Europa, 88100, Catanzaro, Italy; Net4Science srl, Università "Magna Græcia", Campus Salvatore Venuta, Viale Europa, 88100, Catanzaro, Italy
| | - Stefano Alcaro
- Dipartimento di Scienze della Salute, Università "Magna Græcia", Campus Salvatore Venuta, Viale Europa, 88100, Catanzaro, Italy; Net4Science srl, Università "Magna Græcia", Campus Salvatore Venuta, Viale Europa, 88100, Catanzaro, Italy
| | - Antonio Lupia
- Dipartimento di Scienze della Salute, Università "Magna Græcia", Campus Salvatore Venuta, Viale Europa, 88100, Catanzaro, Italy; Net4Science srl, Università "Magna Græcia", Campus Salvatore Venuta, Viale Europa, 88100, Catanzaro, Italy
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Wang J, Liu Q, Xiao H, Luo X, Liu X. Suppressive effects of Momordin Ic on HepG2 cell migration and invasion by regulating MMP-9 and adhesion molecules: Involvement of p38 and JNK pathways. Toxicol In Vitro 2019; 56:75-83. [DOI: 10.1016/j.tiv.2019.01.007] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2018] [Revised: 01/09/2019] [Accepted: 01/11/2019] [Indexed: 10/27/2022]
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Ghasemi A, Saeidi J, Azimi-Nejad M, Hashemy SI. Leptin-induced signaling pathways in cancer cell migration and invasion. Cell Oncol (Dordr) 2019; 42:243-260. [PMID: 30877623 DOI: 10.1007/s13402-019-00428-0] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/06/2019] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Increasing evidence indicates that obesity is associated with tumor development and progression. Leptin is an adipocyte-related hormone with a key role in energy metabolism and whose circulating levels are elevated in obesity. The effect of leptin on cancer progression and metastasis and its underlying mechanisms are still unclear. Leptin can impact various steps in tumor metastasis, including epithelial-mesenchymal transition, cell adhesion to the extracellular matrix (ECM), and proteolysis of ECM components. To do so, leptin binds to its receptor (OB-Rb) to activate signaling pathways and downstream effectors that participate in tumor cell invasion as well as distant metastasis. CONCLUSIONS In this review, we describe metastasis steps in detail and characterize metastasis-related molecules activated by leptin, which may help to develop a roadmap that guides future work. In addition, we conclude that a profound understanding of the fundamental molecular processes that contribute to leptin-induced metastasis may pave the way for the development of new prognostic molecules and appropriate approaches to the treatment of obesity-related cancers.
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Affiliation(s)
- Ahmad Ghasemi
- Department of Basic Medical Sciences, Neyshabur University of Medical Sciences, Neyshabur, Iran
- Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Jafar Saeidi
- Department of Physiology, School of Basic Science, Neyshabur Branch, Islamic Azad University, Neyshabur, Iran
| | - Mohsen Azimi-Nejad
- Department of Basic Medical Sciences, Neyshabur University of Medical Sciences, Neyshabur, Iran
- Department of Genetic, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Seyed Isaac Hashemy
- Surgical Oncology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
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Costea T, Hudiță A, Ciolac OA, Gălățeanu B, Ginghină O, Costache M, Ganea C, Mocanu MM. Chemoprevention of Colorectal Cancer by Dietary Compounds. Int J Mol Sci 2018; 19:E3787. [PMID: 30487390 PMCID: PMC6321468 DOI: 10.3390/ijms19123787] [Citation(s) in RCA: 57] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2018] [Revised: 11/18/2018] [Accepted: 11/23/2018] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer is one of the leading causes of death, and the third most diagnosed type of cancer, worldwide. It is most common amongst men and women over 50 years old. Risk factors include smoking, alcohol, diet, physical inactivity, genetics, alterations in gut microbiota, and associated pathologies (diabetes, obesity, chronic inflammatory bowel diseases). This review will discuss, in detail, the chemopreventive properties of some dietary compounds (phenolic compounds, carotenoids, iridoids, nitrogen compounds, organosulfur compounds, phytosterols, essential oil compounds, polyunsaturated fatty acids and dietary fiber) against colorectal cancer. We present recent data, focusing on in vitro, laboratory animals and clinical trials with the previously mentioned compounds. The chemopreventive properties of the dietary compounds involve multiple molecular and biochemical mechanisms of action, such as inhibition of cell growth, inhibition of tumor initiation, inhibition of adhesion, migration and angiogenesis, apoptosis, interaction with gut microbiota, regulation of cellular signal transduction pathways and xenobiotic metabolizing enzymes, etc. Moreover, this review will also focus on the natural dietary compounds' bioavailability, their synergistic protective effect, as well as the association with conventional therapy. Dietary natural compounds play a major role in colorectal chemoprevention and continuous research in this field is needed.
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Affiliation(s)
- Teodora Costea
- Department of Pharmacognosy, Phytochemistry and Phytotherapy, "Carol Davila" University of Medicine and Pharmacy, 020956 Bucharest, Romania.
| | - Ariana Hudiță
- Department of Biochemistry and Molecular Biology, University of Bucharest, 050095 Bucharest, Romania.
| | - Oana-Alina Ciolac
- Department of Biophysics, "Carol Davila" University of Medicine and Pharmacy, 050474 Bucharest, Romania.
| | - Bianca Gălățeanu
- Department of Biochemistry and Molecular Biology, University of Bucharest, 050095 Bucharest, Romania.
| | - Octav Ginghină
- Department of Surgery, "Sf. Ioan" Emergency Clinical Hospital, 042122 Bucharest, Romania.
- Department II, Faculty of Dental Medicine, "Carol Davila" University of Medicine and Pharmacy, 030167 Bucharest, Romania.
| | - Marieta Costache
- Department of Biochemistry and Molecular Biology, University of Bucharest, 050095 Bucharest, Romania.
| | - Constanța Ganea
- Department of Biophysics, "Carol Davila" University of Medicine and Pharmacy, 050474 Bucharest, Romania.
| | - Maria-Magdalena Mocanu
- Department of Biophysics, "Carol Davila" University of Medicine and Pharmacy, 050474 Bucharest, Romania.
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Pandurangan AK, Divya T, Kumar K, Dineshbabu V, Velavan B, Sudhandiran G. Colorectal carcinogenesis: Insights into the cell death and signal transduction pathways: A review. World J Gastrointest Oncol 2018; 10:244-259. [PMID: 30254720 PMCID: PMC6147765 DOI: 10.4251/wjgo.v10.i9.244] [Citation(s) in RCA: 56] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2018] [Revised: 06/05/2018] [Accepted: 06/28/2018] [Indexed: 02/05/2023] Open
Abstract
Colorectal carcinogenesis (CRC) imposes a major health burden in developing countries. It is the third major cause of cancer deaths. Despite several treatment strategies, novel drugs are warranted to reduce the severity of this disease. Adenomatous polyps in the colon are the major culprits in CRC and found in 45% of cancers, especially in patients 60 years of age. Inflammatory polyps are currently gaining attention in CRC, and a growing body of evidence denotes the role of inflammation in CRC. Several experimental models are being employed to investigate CRC in animals, which include the APCmin/+ mouse model, Azoxymethane, Dimethyl hydrazine, and a combination of Dextran sodium sulphate and dimethyl hydrazine. During CRC progression, several signal transduction pathways are activated. Among the major signal transduction pathways are p53, Transforming growth factor beta, Wnt/β-catenin, Delta Notch, Hippo signalling, nuclear factor erythroid 2-related factor 2 and Kelch-like ECH-associated protein 1 pathways. These signalling pathways collaborate with cell death mechanisms, which include apoptosis, necroptosis and autophagy, to determine cell fate. Extensive research has been carried out in our laboratory to investigate these signal transduction and cell death mechanistic pathways in CRC. This review summarizes CRC pathogenesis and the related cell death and signal transduction pathways.
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Affiliation(s)
- Ashok kumar Pandurangan
- Cell Biology Laboratory, Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600025, India
- School of Life sciences, B.S. Abdur Rahman Crescent Institute of Science and Technology, Chennai 600048, India
| | - Thomas Divya
- Cell Biology Laboratory, Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600025, India
| | - Kalaivani Kumar
- School of Life sciences, B.S. Abdur Rahman Crescent Institute of Science and Technology, Chennai 600048, India
| | - Vadivel Dineshbabu
- Cell Biology Laboratory, Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600025, India
| | - Bakthavatchalam Velavan
- Cell Biology Laboratory, Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600025, India
| | - Ganapasam Sudhandiran
- Cell Biology Laboratory, Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600025, India
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Li D, Li L, Xiao N, Li M, Xie X. Physical properties of oil-in-water nanoemulsions stabilized by OSA-modified starch for the encapsulation of lycopene. Colloids Surf A Physicochem Eng Asp 2018. [DOI: 10.1016/j.colsurfa.2018.04.055] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
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Park B, Lim JW, Kim H. Lycopene treatment inhibits activation of Jak1/Stat3 and Wnt/β-catenin signaling and attenuates hyperproliferation in gastric epithelial cells. Nutr Res 2018; 70:70-81. [PMID: 30098838 DOI: 10.1016/j.nutres.2018.07.010] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2018] [Revised: 07/05/2018] [Accepted: 07/19/2018] [Indexed: 12/19/2022]
Abstract
Helicobacter pylori (H pylori) colonizes the human stomach and increases the risk of gastric diseases including gastric cancer. H pylori increases reactive oxygen species (ROS), which activate Janus-activator kinase 1 (Jak1)/signal transducers and activators of transcription 3 (Stat3) in gastric epithelial cells. ROS mediate hyperproliferation, a hallmark of carcinogenesis, by activating Wnt/β-catenin signaling in various cells. Lycopene is a potent antioxidant exhibiting anticancer effects. We hypothesized that lycopene may inhibit H pylori-induced hyperproliferation by suppressing ROS-mediated activation of Jak1/Stat3 and Wnt/β-catenin signaling, and β-catenin target gene expression in gastric epithelial cells. We determined cell viability, ROS levels, and the protein levels of phospho- and total Jak1/Stat3, Wnt/β-catenin signaling molecules, Wnt-1, lipoprotein-related protein 5, and β-catenin target oncogenes (c-Myc and cyclin E) in H pylori-infected gastric epithelial AGS cells. The Jak1/Stat3 inhibitor AG490 served as the control treatment. The significance of the differences among groups was calculated using the 1-way analysis of variance followed by Newman-Keuls post hoc tests. The results show that lycopene reduced ROS levels and inhibited Jak1/Stat3 activation, alteration of Wnt/β-catenin multiprotein complex molecules, expression of c-Myc and cyclin E, and cell proliferation in H pylori-infected AGS cells. AG490 similarly inhibited H pylori-induced cell proliferation, alteration of Wnt/β-catenin multiprotein complex molecules, and oncogene expression. H pylori increased the levels of Wnt-1 and its receptor lipoprotein-related protein 5; this increase was inhibited by either lycopene or AG490 in AGS cells. In conclusion, lycopene inhibits ROS-mediated activation of Jak1/Stat3 and Wnt/β-catenin signaling and, thus, oncogene expression in relation to hyperproliferation in H pylori-infected gastric epithelial cells. Lycopene might be a potential and promising nutrient for preventing H pylori-associated gastric diseases including gastric cancer.
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Affiliation(s)
- Bohye Park
- Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul 03722, Korea.
| | - Joo Weon Lim
- Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul 03722, Korea.
| | - Hyeyoung Kim
- Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul 03722, Korea.
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Yen GC, Tsai CM, Lu CC, Weng CJ. Recent progress in natural dietary non-phenolic bioactives on cancers metastasis. J Food Drug Anal 2018; 26:940-964. [PMID: 29976413 PMCID: PMC9303016 DOI: 10.1016/j.jfda.2018.05.003] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2018] [Revised: 05/04/2018] [Accepted: 05/15/2018] [Indexed: 12/20/2022] Open
Abstract
From several decades ago to now, cancer continues to be the leading cause of death worldwide, and metastasis is the major cause of cancer-related deaths. For health benefits, there is a great desire to use non-chemical therapy such as nutraceutical supplementation to prevent pathology development. Over 10,000 different natural bioactives or phytochemicals have been known that possessing potential preventive or supplementary effects for various diseases including cancer. Previously, the in vitro and in vivo anti-invasive and anti-metastatic activities of phenolic acids, monophenol, polyphenol and their derivatives and flavonoids and their derivatives have been reviewed. However, a vast number of natural dietary compounds other than phenolics have been demonstrated to potentially possess the ability to inhibit the invasion and metastasis of various cancers. In this review, we summarize the studies in recent decade on in vitro and in vivo effects and molecular mechanisms of natural bioactives, excluding the phenolics in food, in cancer invasion and metastasis. By combining this review of non-phenolics with the previous phenolics reviews, the puzzle for the contribution of natural dietary bioactives on cancer invasive or/and metastatic progress will be almost complete and more clear.
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Affiliation(s)
- Gow-Chin Yen
- Department of Food Science and Biotechnology, National Chung Hsing University, Taichung, Taiwan; Graduate Institute of Food Safety, National Chung Hsing University, Taichung, Taiwan
| | - Chiung-Man Tsai
- Tainan Hospital, Ministry of Health and Welfare, Tainan City, Taiwan
| | - Chi-Cheng Lu
- Department of Pharmacy, Buddhist Tzu Chi General Hospital, Hualien, Taiwan
| | - Chia-Jui Weng
- Department of Living Services Industry, Tainan University of Technology, Tainan City, Taiwan.
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Sahin K, Yenice E, Tuzcu M, Orhan C, Mizrak C, Ozercan IH, Sahin N, Yilmaz B, Bilir B, Ozpolat B, Kucuk O. Lycopene Protects Against Spontaneous Ovarian Cancer Formation in Laying Hens. J Cancer Prev 2018; 23:25-36. [PMID: 29629346 PMCID: PMC5886492 DOI: 10.15430/jcp.2018.23.1.25] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2018] [Revised: 03/09/2018] [Accepted: 03/09/2018] [Indexed: 12/16/2022] Open
Abstract
Background Dietary intake of lycopene has been associated with a reduced risk of ovarian cancer, suggesting its chemopreventive potential against ovarian carcinogenesis. Lycopene's molecular mechanisms of action in ovarian cancer have not been fully understood. Therefore, in the present study, we investigated the effects of lycopene on the ovarian cancer formation using the laying hen model, a biologically relevant animal model of spontaneous ovarian carcinogenesis due to high incidence rates similar to humans. Methods In this study, a total of 150 laying hens at age of 102 weeks were randomized into groups of 50: a control group (0 mg of lycopene per kg of diet) and two treatment groups (200 mg or 400 mg of lycopene per kg of diet, or ~26 and 52 mg/d/hen, respectively). At the end of 12 months, blood, ovarian tissues and tumors were collected. Results We observed that lycopene supplementation significantly reduced the overall ovarian tumor incidence (P < 0.01) as well as the number and the size of the tumors (P < 0.004 and P < 0.005, respectively). Lycopene also significantly decreased the rate of adenocarcinoma, including serous and mucinous subtypes (P < 0.006). Moreover, we also found that the serum level of oxidative stress marker malondialdehyde was significantly lower in lycopene-fed hens compared to control birds (P < 0.001). Molecular analysis of the ovarian tumors revealed that lycopene reduced the expression of NF-κB while increasing the expression of nuclear factor erythroid 2 and its major target protein, heme oxygenase 1. In addition, lycopene supplementation decreased the expression of STAT3 by inducing the protein inhibitor of activated STAT3 expression in the ovarian tissues. Conclusions Taken together, our findings strongly support the potential of lycopene in the chemoprevention of ovarian cancer through antioxidant and anti-inflammatory mechanisms.
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Affiliation(s)
- Kazim Sahin
- Department of Animal Nutrition, Faculty of Veterinary Science, Firat University, Elazig, Turkey
| | | | - Mehmet Tuzcu
- Division of Biology, Faculty of Science, Firat University, Elazig, Turkey
| | - Cemal Orhan
- Department of Animal Nutrition, Faculty of Veterinary Science, Firat University, Elazig, Turkey
| | | | - Ibrahim H Ozercan
- Department of Pathology, Faculty of Medicine, Firat University, Elazig, Turkey
| | - Nurhan Sahin
- Department of Animal Nutrition, Faculty of Veterinary Science, Firat University, Elazig, Turkey
| | - Bahiddin Yilmaz
- Winship Cancer Institute of Emory University, Atlanta, GA, USA
| | - Birdal Bilir
- Winship Cancer Institute of Emory University, Atlanta, GA, USA
| | - Bulent Ozpolat
- Department of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Omer Kucuk
- Winship Cancer Institute of Emory University, Atlanta, GA, USA
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Bansal M, Singh N, Pal S, Dev I, Ansari KM. Chemopreventive Role of Dietary Phytochemicals in Colorectal Cancer. ADVANCES IN MOLECULAR TOXICOLOGY 2018. [DOI: 10.1016/b978-0-444-64199-1.00004-x] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Namani A, Li J, Wang XJ, Tang X. A Review of Compounds for Prevention of Colorectal Cancer. ACTA ACUST UNITED AC 2017. [DOI: 10.1007/s40495-017-0101-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Lei Z, Zhang H, Wang Y, Meng X, Wang Z. Peptide Microarray-Based Metal Enhanced Fluorescence Assay for Multiple Profiling of Matrix Metalloproteinases Activities. Anal Chem 2017; 89:6749-6757. [DOI: 10.1021/acs.analchem.7b01037] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Affiliation(s)
- Zhen Lei
- State Key Laboratory
of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, P. R. China
- University of Chinese Academy of Sciences, Beijing 100049, P. R. China
| | - Hua Zhang
- State Key Laboratory
of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, P. R. China
| | - Yaoqi Wang
- Department
of Thyroid Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P. R. China
| | - Xianying Meng
- Department
of Thyroid Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P. R. China
| | - Zhenxin Wang
- State Key Laboratory
of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, P. R. China
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Cha JH, Kim WK, Ha AW, Kim MH, Chang MJ. Anti-inflammatory effect of lycopene in SW480 human colorectal cancer cells. Nutr Res Pract 2017; 11:90-96. [PMID: 28386381 PMCID: PMC5376536 DOI: 10.4162/nrp.2017.11.2.90] [Citation(s) in RCA: 61] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2016] [Revised: 08/07/2016] [Accepted: 11/22/2016] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND/OBJECTIVES Although the antioxidative effects of lycopene are generally known, the molecular mechanisms underlying the anti-inflammatory properties of lycopene are not fully elucidated. This study aimed to examine the role and mechanism of lycopene as an inhibitor of inflammation. METHODS/MATERIALS Lipopolysaccharide (LPS)-stimulated SW 480 human colorectal cancer cells were treated with 0, 10, 20, and 30 µM lycopene. The MTT assay was performed to determine the effects of lycopene on cell proliferation. Western blotting was performed to observe the expression of inflammation-related proteins, including nuclear factor-kappa B (NF-κB), inhibitor kappa B (IκB), mitogen-activated protein kinase (MAPK), extracellular signal-related kinase (ERK), c-jun NH2-terminal kinase (JNK), and p38 (p38 MAP kinase). Real-time polymerase chain reaction was performed to investigate the mRNA expression of tumor necrosis factor α (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). Concentrations of nitric oxide (NO) and prostaglandin E2 (PGE2) were determined via enzyme-linked immunosorbent assays. RESULTS In cells treated with lycopene and LPS, the mRNA expression of TNF-α, IL-1β, IL-6, iNOS, and COX-2 were decreased significantly in a dose-dependent manner (P < 0.05). The concentrations of PGE2 and NO decreased according to the lycopene concentration (P < 0.05). The protein expressions of NF-κB and JNK were decreased significantly according to lycopene concertation (P < 0.05). CONCLUSIONS Lycopene restrains NF-κB and JNK activation, which causes inflammation, and suppresses the expression of TNF-α, IL-1β, IL-6, COX-2, and iNOS in SW480 human colorectal cancer cells.
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Affiliation(s)
- Jae Hoon Cha
- Department of Food Science and Nutrition, Dankook University, Gyeonggi 16890, Korea
| | - Woo Kyoung Kim
- Department of Food Science and Nutrition, Dankook University, Gyeonggi 16890, Korea
| | - Ae Wha Ha
- Department of Food Science and Nutrition, Dankook University, Gyeonggi 16890, Korea
| | - Myung Hwan Kim
- Department of Food Engineering, Dankook University, Chungnam 31116, Korea
| | - Moon Jeong Chang
- Department of Food and Nutrition, Kookmin University, 77 Jeongneung-Ro, Seongbuk-gu, Seoul 02707, Korea
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Terpenoids as anti-colon cancer agents - A comprehensive review on its mechanistic perspectives. Eur J Pharmacol 2016; 795:169-178. [PMID: 27940056 DOI: 10.1016/j.ejphar.2016.12.008] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2016] [Revised: 12/05/2016] [Accepted: 12/05/2016] [Indexed: 02/06/2023]
Abstract
Multistep model of colon carcinogenesis has provided the framework to advance our understanding of the molecular basis of colon cancer. This multistage process of carcinogenesis takes a long period to transform from a normal epithelial cell to invasive carcinoma. Thus, it provides enough time to intervene the process of carcinogenesis especially through dietary modification. In spite of the in-depth understanding of the colon cancer etiology and pathophysiology and its association with diet, colon cancer remains a major cause of cancer mortality worldwide. Phytochemicals and their derivatives are gaining attention in cancer prevention and treatment strategies because of cancer chemotherapy associated adverse effects. Being the largest group of phytochemicals traditionally used for medicinal purpose in India and China, terpenoids are recently being explored as anticancer agents. Anticancer properties of terpenoids are associated with various mechanisms like counteraction of oxidative stress, potentiating endogenous antioxidants, improving detoxification potential, disrupting cell survival pathways and inducing apoptosis. This review gives a comprehensive idea of naturally occurring terpenoids as useful agents for the prevention of colon cancer with reference to their classes, sources and molecular targets. Based on the explored molecular targets further research in colon cancer chemoprevention is warranted.
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Wang X, Yang HH, Liu Y, Zhou Q, Chen ZH. Lycopene Consumption and Risk of Colorectal Cancer: A Meta-Analysis of Observational Studies. Nutr Cancer 2016; 68:1083-96. [DOI: 10.1080/01635581.2016.1206579] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
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Fan Y, Gan Y, Shen Y, Cai X, Song Y, Zhao F, Yao M, Gu J, Tu H. Leptin signaling enhances cell invasion and promotes the metastasis of human pancreatic cancer via increasing MMP-13 production. Oncotarget 2016; 6:16120-34. [PMID: 25948792 PMCID: PMC4599260 DOI: 10.18632/oncotarget.3878] [Citation(s) in RCA: 73] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2015] [Accepted: 03/31/2015] [Indexed: 02/07/2023] Open
Abstract
Emerging evidence has suggested that leptin, an adipokine related to energy homeostasis, plays a role in cancer growth and metastasis. However, its impact on pancreatic cancer is rarely studied. In this study, we found that leptin's functional receptor Ob-Rb was expressed in pancreatic cancer cell lines. Treatment with leptin enhanced the migration and invasion of pancreatic cancer cells but did not affect the proliferation of human pancreatic cancer cells. Leptin up-regulated the expression of matrix metalloproteinase-13 (MMP-13) via the JAK2/STAT3 signaling pathway. The overexpression of leptin was shown to significantly promote tumor growth and lymph node metastasis in a subcutaneous model and an orthotopic model of human pancreatic cancer, respectively. Furthermore, in human pancreatic cancer tissues, the expression of Ob-Rb was positively correlated with the MMP-13 level. The increased expression of either Ob-Rb or MMP-13 was significantly associated with lymph node metastasis and tended to be associated with the TNM stage in patients with pancreatic cancer. Our findings suggest that leptin enhances the invasion of pancreatic cancer through the increase in MMP-13 production, and targeting the leptin/MMP-13 axis could be an attractive therapeutic strategy for pancreatic cancer.
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Affiliation(s)
- Yingchao Fan
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yu Gan
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yuling Shen
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Department of Head and Neck Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaojin Cai
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yanfang Song
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Fangyu Zhao
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ming Yao
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jianren Gu
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hong Tu
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Ko EY, Moon A. Natural Products for Chemoprevention of Breast Cancer. J Cancer Prev 2015; 20:223-31. [PMID: 26734584 PMCID: PMC4699749 DOI: 10.15430/jcp.2015.20.4.223] [Citation(s) in RCA: 85] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2015] [Revised: 11/26/2015] [Accepted: 11/30/2015] [Indexed: 11/20/2022] Open
Abstract
Breast cancer is the primary cause of cancer death in women. Although current therapies have shown some promise against breast cancer, there is still no effective cure for the majority of patients in the advanced stages of breast cancer. Development of effective agents to slow, reduce, or reverse the incidence of breast cancer in high-risk women is necessary. Chemoprevention of breast cancer by natural products is advantageous, as these compounds have few side effects and low toxicity compared to synthetic compounds. In the present review, we summarize natural products which exert chemopreventive activities against breast cancer, such as curcumin, sauchinone, lycopene, denbinobin, genipin, capsaicin, and ursolic acid. This review examines the current knowledge about natural compounds and their mechanisms that underlie breast cancer chemopreventive activity both in vitro and in vivo. The present review may provide information on the use of these compounds for the prevention of breast cancer.
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Affiliation(s)
- Eun-Yi Ko
- College of Pharmacy, Duksung Women’s University, Seoul,
Korea
| | - Aree Moon
- College of Pharmacy, Duksung Women’s University, Seoul,
Korea
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Hibino Y, Sakamoto N, Naito Y, Goto K, Oo HZ, Sentani K, Hinoi T, Ohdan H, Oue N, Yasui W. Significance of miR-148a in Colorectal Neoplasia: Downregulation of miR-148a Contributes to the Carcinogenesis and Cell Invasion of Colorectal Cancer. Pathobiology 2015; 82:233-41. [PMID: 26389729 DOI: 10.1159/000438826] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2015] [Accepted: 07/20/2015] [Indexed: 11/19/2022] Open
Abstract
OBJECTIVE Colorectal cancer (CRC) develops through the deregulation of gene expression and the accumulation of epigenetic abnormalities, leading to tumor cell acquisition of malignant features. MicroRNAs (miRNAs) play a critical role in cancer development, where they can act as oncogenes or oncosuppressors. METHODS miR-148a expression was measured by qRT-PCR in patients with colorectal adenoma (n = 21) and CRC (stage I-IV, n = 159) using formalin-fixed paraffin-embedded tissue samples. In situ hybridization (ISH) using an miR-148a-specific probe was also performed. To further confirm the direct effect of miR-148a on matrix metalloproteinase (MMP)7 expression in CRC, MTT and cell invasion assays using HT29 and WiDr cells were performed. RESULTS miR-148a expression was found to be clearly downregulated in high-grade adenoma compared to low-grade adenoma on both qRT-PCR and ISH analysis. Downregulation of miR-148a expression was significantly correlated with advanced clinicopathological features and was an independent prognostic classifier in patients with stage III CRC. In CRC cells and tissues, miR-148a expression was inversely correlated with the expression of MMP7. CONCLUSION We showed the collaborative participation of miR-148a and MMP7 in CRC cell invasion. These results also demonstrate that the downregulation of miR-148a expression promotes CRC progression, especially carcinogenesis and cancer cell invasion.
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Affiliation(s)
- Yumi Hibino
- Department of Molecular Pathology, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
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Rotelli MT, Bocale D, De Fazio M, Ancona P, Scalera I, Memeo R, Travaglio E, Zbar AP, Altomare DF. IN-VITRO evidence for the protective properties of the main components of the Mediterranean diet against colorectal cancer: A systematic review. Surg Oncol 2015; 24:145-52. [PMID: 26303826 DOI: 10.1016/j.suronc.2015.08.001] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2014] [Revised: 07/21/2015] [Accepted: 08/04/2015] [Indexed: 02/07/2023]
Abstract
AIM Epidemiological studies have shown that the incidence and mortality rates of colorectal cancer (CRC) vary over 10-fold worldwide where within Westernized societies lower rates are observed amongst populations living within the Mediterranean basin, suggesting a significant influence of environment and dietary style in CRC carcinogenesis. Interpretation of the data concerning the benefits of mediterranean (MD) diet is difficult in vivo because of the variability of alimentary regimens used, the differing compliance with dietary supplementation and because of the non-uniform duration of patient cohort observation. Therefore, the aim of this review is to evaluate the in-vitro effects on colorectal cancer cell lines. METHODS the literature concerning the in-vitro effects of 4 of the principal components symbolizing the MD such as olive oil (polyphenol), red chili (capsaicin), tomato (lycopene) and red grapes (resveratrol) have been systematically reviewed. RESULTS Several studies have demonstrated that polyphenols form olive oil, lycopene, resveratrol and capsaicin have multiple anticancer properties affecting several metabolic pathways involved in cancerogenesis, apoptosis, and metastasis in CRC cell lines. CONCLUSION This review summarizes some of the most recent data potentially supportive of the use of MD in CRC chemoprevention, analyzing the in vitro effects of individual components of the MD on CRC cell development, progression, metastasis and apoptosis.
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Affiliation(s)
- M T Rotelli
- DETO Dept of Emergency and Organ Transplantation, University "Aldo Moro" of Bari, Italy.
| | - D Bocale
- DETO Dept of Emergency and Organ Transplantation, University "Aldo Moro" of Bari, Italy
| | - M De Fazio
- DETO Dept of Emergency and Organ Transplantation, University "Aldo Moro" of Bari, Italy
| | - P Ancona
- DETO Dept of Emergency and Organ Transplantation, University "Aldo Moro" of Bari, Italy
| | - I Scalera
- DETO Dept of Emergency and Organ Transplantation, University "Aldo Moro" of Bari, Italy
| | - R Memeo
- DETO Dept of Emergency and Organ Transplantation, University "Aldo Moro" of Bari, Italy
| | - E Travaglio
- DETO Dept of Emergency and Organ Transplantation, University "Aldo Moro" of Bari, Italy
| | - A P Zbar
- Department of Surgery and Transplantation, Chaim Sheba Medical Center, Israel; Sackler School of Medicine, Tel Aviv University, Israel; Department of Anatomy, School of Medical Sciences, Centre for Bioengineering and Nanomedicine, University of Otago, Dunedin, New Zealand
| | - D F Altomare
- DETO Dept of Emergency and Organ Transplantation, University "Aldo Moro" of Bari, Italy
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Kashino I, Mizoue T, Tanaka K, Tsuji I, Tamakoshi A, Matsuo K, Wakai K, Nagata C, Inoue M, Tsugane S, Sasazuki S. Vegetable consumption and colorectal cancer risk: an evaluation based on a systematic review and meta-analysis among the Japanese population. Jpn J Clin Oncol 2015; 45:973-9. [PMID: 26450957 DOI: 10.1093/jjco/hyv111] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2015] [Accepted: 06/28/2015] [Indexed: 12/23/2022] Open
Abstract
OBJECTIVE The association between vegetable consumption and colorectal cancer risk remains unclear and may differ by region. We performed a systematic review and meta-analysis of epidemiologic studies on this issue among the Japanese population. METHODS A systematic review and meta-analysis was performed by searching MEDLINE through PubMed and the Ichushi database for cohort and case-control studies that were published by the end of December 2014. Associations were evaluated based on their magnitude and the strength of the evidence. Meta-analysis was performed by using the random effects model to estimate the summary relative risk with 95% confidence interval according to the study design. The final judgment was made based on a consensus of the research group members with consideration for both epidemiological evidence and biological plausibility. RESULTS We identified six cohort studies and 11 case-control studies on vegetable intake and colorectal cancer among the Japanese population. Of the cohort studies, one study showed a weak inverse association with colon cancer and another study showed a weak positive association with rectal cancer in men, but other studies found no associations between vegetable consumption and colon and rectal cancers. With regard to case-control studies, one study found a strong inverse association with colon cancer, and three studies showed a weak-to-strong inverse association with rectal cancer. In meta-analysis, the summary relative risk (95% confidence interval) for the highest vs. the lowest categories of vegetable consumption were 1.00 (0.92-1.10) and 0.75 (0.59-0.96) for cohort and case-control studies, respectively. CONCLUSIONS There was insufficient evidence to support an association between intake of vegetables and the risk of colorectal cancer among the Japanese population.
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Affiliation(s)
- Ikuko Kashino
- Department of Epidemiology and Prevention, Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo
| | - Tetsuya Mizoue
- Department of Epidemiology and Prevention, Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo
| | - Keitaro Tanaka
- Department of Preventive Medicine, Faculty of Medicine, Saga University, Saga
| | - Ichiro Tsuji
- Division of Epidemiology, Department of Public Health and Forensic Medicine, Tohoku University Graduate School of Medicine, Sendai
| | - Akiko Tamakoshi
- Department of Public Health, Hokkaido University Graduate School of Medicine, Sapporo
| | - Keitaro Matsuo
- Department of Preventive Medicine, Kyushu University Faculty of Medical Sciences, Fukuoka
| | - Kenji Wakai
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya
| | - Chisato Nagata
- Department of Epidemiology and Preventive Medicine, Gifu University Graduate School of Medicine, Gifu
| | - Manami Inoue
- Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo AXA Department of Health and Human Security, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Shoichiro Tsugane
- Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo
| | - Shizuka Sasazuki
- Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo
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