|
1
|
Navin AK, Rejani CT, Chandrasekaran B, Tyagi A. Urolithins: Emerging natural compound targeting castration-resistant prostate cancer (CRPC). Biomed Pharmacother 2025; 187:118058. [PMID: 40253830 DOI: 10.1016/j.biopha.2025.118058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2025] [Revised: 04/03/2025] [Accepted: 04/14/2025] [Indexed: 04/22/2025] Open
Abstract
Castration-resistant prostate cancer (CRPC) presents a significant challenge due to its resistance to conventional androgen deprivation therapies. Urolithins, bioactive metabolites derived from ellagitannins, have recently emerged as promising therapeutic agents for CRPC. Urolithins not only inhibit androgen receptor (AR) signaling, a crucial factor in the progression of CRPC, but also play a key role in regulating oxidative stress by their antioxidant properties, thereby inhibiting increased reactive oxygen species, a common feature of the aggressive nature of CRPC. Research has shown that urolithins induce apoptosis and diminish pro-survival signaling, leading to tumor inhibition. This review delves into the intricate mechanisms through which urolithins exert their therapeutic effects, focusing on both AR-dependent and AR-independent pathways. It also explores the exciting potential of combining urolithins with androgen ablation therapy, opening new avenues for CRPC treatment.
Collapse
Affiliation(s)
- Ajit Kumar Navin
- Department of Pharmacology, College of Pharmacy, Texas A&M University, College Station, TX 77845, USA
| | | | - Balaji Chandrasekaran
- Department of Pharmacology, College of Pharmacy, Texas A&M University, College Station, TX 77845, USA
| | - Ashish Tyagi
- Department of Pharmacology, College of Pharmacy, Texas A&M University, College Station, TX 77845, USA.
| |
Collapse
|
|
2
|
Chan C, Tsai Y, Lu T, Liao Y, Hsieh S. Functional Evaluation of Cooking-Mimicking Extracts From Chinese Olive ( Canarium album L.) Leaves, Fruits, and Pits Using Cell-Based and In Silico Analysis. Food Sci Nutr 2025; 13:e70337. [PMID: 40444125 PMCID: PMC12121516 DOI: 10.1002/fsn3.70337] [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: 10/24/2024] [Revised: 05/05/2025] [Accepted: 05/11/2025] [Indexed: 06/02/2025] Open
Abstract
Chinese olive (CO; Canarium album L.) fruits are rich in phytochemicals with known physiological benefits. However, most studies evaluating the effects of CO have used ethyl acetate, acetone, and chloroform as the extraction solvents, which do not accurately reflect real dietary conditions. Moreover, research on CO leaves and pits remains limited. This study investigated the functional properties of extracts derived from CO leaves, fruits, and pits, prepared under simulated conventional culinary and dietary conditions (including solvents, extract combinations, and heat treatment), referred to as cooking-mimicking extracts. Our results revealed that most CO extracts reduced the production of nitric oxide in lipopolysaccharide-stimulated RAW264.7 macrophages and inhibited the proliferation of HCT116 colorectal cancer cells. Combinations of water-soluble CO extracts exerted a synergistic effect, suppressing cancer cell proliferation. To the best of our knowledge, this study is the first to identify methylellagic acid deoxyhexoside, vitexin 2-O-rhamnoside, and isovitexin 2-O-rhamnoside in CO extracts. Molecular docking predicted strong interactions with phosphofructokinase (PFK), a key glycolytic enzyme implicated in cancer cell proliferation. Treatment with CO extracts, including heat-treated forms, markedly reduced PFK activity and cell viability in HCT116 cells. These findings provide new insights into the bioactive constituents and physiological functions of CO extracts, supporting their potential application in dietotherapy.
Collapse
Affiliation(s)
- Chun‐Wai Chan
- Institute of Food Science and Technology, College of Bioresources and AgricultureNational Taiwan UniversityTaipeiTaiwan
| | - Yu‐Jo Tsai
- Institute of Food Science and Technology, College of Bioresources and AgricultureNational Taiwan UniversityTaipeiTaiwan
| | - Ting‐Jang Lu
- Institute of Food Science and Technology, College of Bioresources and AgricultureNational Taiwan UniversityTaipeiTaiwan
| | - Yi‐Chun Liao
- Department of Biochemical Science and Technology, College of Life ScienceNational Taiwan UniversityTaipeiTaiwan
| | - Shu‐Chen Hsieh
- Institute of Food Science and Technology, College of Bioresources and AgricultureNational Taiwan UniversityTaipeiTaiwan
| |
Collapse
|
|
3
|
Sun MX, Zhu HC, Yu Y, Yao Y, Li HY, Feng FB, Wang QY, Liu RJ, Sun CG. Role of the Wnt signaling pathway in the complex microenvironment of breast cancer and prospects for therapeutic potential (Review). Int J Oncol 2025; 66:36. [PMID: 40145557 PMCID: PMC12068849 DOI: 10.3892/ijo.2025.5742] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2024] [Accepted: 03/10/2025] [Indexed: 03/28/2025] Open
Abstract
The focus on breast cancer treatment has shifted from the cytotoxic effects of single drugs on tumor cells to multidimensional multi‑pathway synergistic intervention strategies targeting the tumor microenvironment (TME). The activation of the Wnt signaling pathway in the TME of breast cancer cells serves a key regulatory role in tissue homeostasis and is a key driver of the carcinogenic process. Modulating the crosstalk between the Wnt pathway and TME of breast cancer is key for understanding the biological behavior of breast cancer and advancing the development of novel antitumor drugs. The present review aimed to summarize the complex mechanisms of the Wnt signaling pathway in the breast cancer TME, interactions between the Wnt signaling pathway and components of the breast cancer TME and breast cancer‑associated genes, as well as the interactions between the Wnt signaling pathway and other signaling cascades at the molecular level. Furthermore, the present review aimed to highlight the unique advantages of the Wnt signaling pathway in the macro‑regulation of the TME and the current therapeutic strategies targeting the Wnt signaling pathway, their potential clinical value and future research directions in breast cancer treatment.
Collapse
Affiliation(s)
- Meng Xuan Sun
- College of First Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, P.R. China
| | - Han Ci Zhu
- College of First Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, P.R. China
| | - Yang Yu
- State Key Laboratory of Quality Research in Chinese Medicine, and Faculty of Chinese Medicine, Macau University of Science and Technology, Macau 999078, P.R. China
| | - Yan Yao
- Department of Oncology, Weifang Traditional Chinese Hospital, Weifang, Shandong 261000, P.R. China
| | - Hua Yao Li
- College of Traditional Chinese Medicine, Shandong Second Medical University, Weifang, Shandong 261053, P.R. China
| | - Fu Bin Feng
- Department of Oncology, Weifang Traditional Chinese Hospital, Weifang, Shandong 261000, P.R. China
| | - Qing Yang Wang
- College of First Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, P.R. China
| | - Rui Juan Liu
- College of First Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, P.R. China
- Department of Oncology, Weifang Traditional Chinese Hospital, Weifang, Shandong 261000, P.R. China
| | - Chang Gang Sun
- College of First Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, P.R. China
- Department of Oncology, Weifang Traditional Chinese Hospital, Weifang, Shandong 261000, P.R. China
- College of Traditional Chinese Medicine, Shandong Second Medical University, Weifang, Shandong 261053, P.R. China
| |
Collapse
|
|
4
|
Wang K, Hao Z, Xie J, Ma L, Zhang W, Mo J, Li L, Jin C. Nrf2-dependent hepatoprotective effect of ellagic acid in titanium dioxide nanoparticles-induced liver injury. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 135:156064. [PMID: 39306885 DOI: 10.1016/j.phymed.2024.156064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/04/2024] [Revised: 08/11/2024] [Accepted: 09/15/2024] [Indexed: 12/01/2024]
Abstract
BACKGROUND AND AIMS Previous studies suggest that titanium dioxide nanoparticles (TiO2 NPs) induce liver injury, possibly due to oxidative stress and inflammation. Ellagic acid (EA) is a dietary polyphenol extracted from natural sources and possesses antioxidant and anti-inflammatory properties. Nonetheless, the efficacy of EA in mitigating liver injury induced by TiO2 NPs remains to be elucidated. METHODS Primary hepatocytes and L02 cells were cultured with 45 μM EA and 10 μg/ml TiO2 NPs. Mice were orally administered TiO2 NPs (150 mg kg-1) and EA (25/50/100 mg kg-1) for eight weeks. sulforaphane (SFN) as a positive control to evaluate the inhibitory effect of EA on TiO2 NP-induced liver injury (SFN 10 mg kg-1). RNA sequencing (RNA-seq) was employed to elucidate the mechanisms underlying oxidative stress, inflammation, and liver fibrosis. RESULTS We assessed the impact of EA on cytotoxicity, oxidative stress, inflammation, and fibrosis in both cells and mice exposed to TiO2 NPs for an extended period. Our findings indicated that EA had a protective effect on TiO2 NP-exposed hepatocytes, reducing cytotoxicity, oxidative stress, and inflammation. Furthermore, EA treatment markedly reduced serum aminotransferase levels in mice exposed to TiO2 NPs. Furthermore, EA treatment notably reduced hepatic stress response, inflammation, and fibrosis in mice. The treatment of EA demonstrates non-inferiority compared to SFN. The protective effects of EA were attributed to the upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2), EA promoted the translocation and phosphorylation of Nrf2, as indicated by the finding that Nfe2l2 shRNA and inhibition of Nrf2 by ML385 reversed the EA-induced hepatoprotective effects in TiO2 NP-exposed hepatocytes and mice. CONCLUSION EA significantly mitigated liver injury induced by TiO2 NPs. Importantly, we identified that the nuclear translocation and phosphorylation of Nrf2 are the primary mechanisms through which EA alleviates liver injury resulting from exposure to TiO2 NPs. As a natural activator of Nrf2, EA emerges as a promising therapeutic candidate for treating TiO2 NPs-induced liver injury, further enhancing our understanding of its potential as a hepatoprotective agent and its underlying molecular mechanisms.
Collapse
Affiliation(s)
- Kunpeng Wang
- Department of General Surgery, Taizhou Central Hospital (Taizhou University Hospital), Taizhou University, Taizhou, Zhejiang Province, PR China; Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, PR China; General Surgery Laboratory, Renmin Hospital of Wuhan University, Wuhan, 318001, PR China
| | - Zhiqing Hao
- Department of Cell Biology, School of Medicine, Taizhou University, Taizhou, Zhejiang Province, 318001, PR China
| | - Jing Xie
- Department of Pathophysiology, School of Basic Medicine, Shenyang Medical College, Shenyang, Liaoning Province, 110000, PR China
| | - Liman Ma
- Department of Pathophysiology, School of Basic Medicine, Shenyang Medical College, Shenyang, Liaoning Province, 110000, PR China
| | - Weiwei Zhang
- Department of Cell Biology, School of Medicine, Taizhou University, Taizhou, Zhejiang Province, 318001, PR China
| | - Jinggang Mo
- Department of General Surgery, Taizhou Central Hospital (Taizhou University Hospital), Taizhou University, Taizhou, Zhejiang Province, PR China
| | - Lihua Li
- Department of General Surgery, Taizhou Central Hospital (Taizhou University Hospital), Taizhou University, Taizhou, Zhejiang Province, PR China.
| | - Chong Jin
- Department of General Surgery, Taizhou Central Hospital (Taizhou University Hospital), Taizhou University, Taizhou, Zhejiang Province, PR China.
| |
Collapse
|
|
5
|
dos Santos TW, Pereira QC, Fortunato IM, Oliveira FDS, Alvarez MC, Ribeiro ML. Body Composition and Senescence: Impact of Polyphenols on Aging-Associated Events. Nutrients 2024; 16:3621. [PMID: 39519454 PMCID: PMC11547493 DOI: 10.3390/nu16213621] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Revised: 10/16/2024] [Accepted: 10/18/2024] [Indexed: 11/16/2024] Open
Abstract
Aging is a dynamic and progressive process characterized by the gradual accumulation of cellular damage. The continuous functional decline in the intrinsic capacity of living organisms to precisely regulate homeostasis leads to an increased susceptibility and vulnerability to diseases. Among the factors contributing to these changes, body composition-comprised of fat mass and lean mass deposits-plays a crucial role in the trajectory of a disability. Particularly, visceral and intermuscular fat deposits increase with aging and are associated with adverse health outcomes, having been linked to the pathogenesis of sarcopenia. Adipose tissue is involved in the secretion of bioactive factors that can ultimately mediate inter-organ pathology, including skeletal muscle pathology, through the induction of a pro-inflammatory profile such as a SASP, cellular senescence, and immunosenescence, among other events. Extensive research has shown that natural compounds have the ability to modulate the mechanisms associated with cellular senescence, in addition to exhibiting anti-inflammatory, antioxidant, and immunomodulatory potential, making them interesting strategies for promoting healthy aging. In this review, we will discuss how factors such as cellular senescence and the presence of a pro-inflammatory phenotype can negatively impact body composition and lead to the development of age-related diseases, as well as how the use of polyphenols can be a functional measure for restoring balance, maintaining tissue quality and composition, and promoting health.
Collapse
Affiliation(s)
- Tanila Wood dos Santos
- Laboratory of Immunopharmacology and Molecular Biology, Sao Francisco University, Av. Sao Francisco de Assis, 218, Braganca Paulista 12916-900, SP, Brazil; (T.W.d.S.); (Q.C.P.); (I.M.F.); (F.d.S.O.); (M.C.A.)
| | - Quélita Cristina Pereira
- Laboratory of Immunopharmacology and Molecular Biology, Sao Francisco University, Av. Sao Francisco de Assis, 218, Braganca Paulista 12916-900, SP, Brazil; (T.W.d.S.); (Q.C.P.); (I.M.F.); (F.d.S.O.); (M.C.A.)
| | - Isabela Monique Fortunato
- Laboratory of Immunopharmacology and Molecular Biology, Sao Francisco University, Av. Sao Francisco de Assis, 218, Braganca Paulista 12916-900, SP, Brazil; (T.W.d.S.); (Q.C.P.); (I.M.F.); (F.d.S.O.); (M.C.A.)
| | - Fabrício de Sousa Oliveira
- Laboratory of Immunopharmacology and Molecular Biology, Sao Francisco University, Av. Sao Francisco de Assis, 218, Braganca Paulista 12916-900, SP, Brazil; (T.W.d.S.); (Q.C.P.); (I.M.F.); (F.d.S.O.); (M.C.A.)
| | - Marisa Claudia Alvarez
- Laboratory of Immunopharmacology and Molecular Biology, Sao Francisco University, Av. Sao Francisco de Assis, 218, Braganca Paulista 12916-900, SP, Brazil; (T.W.d.S.); (Q.C.P.); (I.M.F.); (F.d.S.O.); (M.C.A.)
- Hematology and Transfusion Medicine Center, University of Campinas/Hemocentro, UNICAMP, Rua Carlos Chagas 480, Campinas 13083-878, SP, Brazil
| | - Marcelo Lima Ribeiro
- Laboratory of Immunopharmacology and Molecular Biology, Sao Francisco University, Av. Sao Francisco de Assis, 218, Braganca Paulista 12916-900, SP, Brazil; (T.W.d.S.); (Q.C.P.); (I.M.F.); (F.d.S.O.); (M.C.A.)
| |
Collapse
|
|
6
|
Qian C, Li H, Hou Z, Liang Z. Effects of different drying methods on Rubus chingii Hu fruit during processing. Heliyon 2024; 10:e24512. [PMID: 38312685 PMCID: PMC10835160 DOI: 10.1016/j.heliyon.2024.e24512] [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: 07/18/2023] [Revised: 01/04/2024] [Accepted: 01/10/2024] [Indexed: 02/06/2024] Open
Abstract
In this study, the dried fruits of Rubus chingii Hu (Chinese name: Fu-Pen-Zi; FPZ) were processed and dried by three methods-in the shade, the sun, and the oven. The composition regarding the standard ingredient, color, and antioxidant capacities were investigated pro- and post-processing. The technique of headspace-solid-phase-microextraction-gas-chromatography-mass spectrometry (HS-SPME-GC-MS) and flavoromics were used to analyze the flavor-conferring metabolites of FPZ. The results obtained revealed that the highest use value and antioxidant capacities were detected in the FPZ fruits processed and dried in the shade. A total of 358 metabolites were detected from them mainly consisting of terpenoids, heterocyclic compounds, and esters. In differential analysis, the down-regulation of the metabolites was much greater than their up-regulation after all three drying methods. In an evaluation of the characteristic compounds and flavors produced after the three methods, there were variations mainly regarding the green and fruity odors. Therefore, considerable insights may be obtained for the development of novel agricultural methods and applications in the pharmaceutical and cosmetic industries by analyzing and comparing the variations in the chemical composition detected pre- and post-processing of the FPZ fruits. This paper provides a scientific basis for quality control in fruits and their clinical applications.
Collapse
Affiliation(s)
- Can Qian
- Key Laboratory of Plant Secondary Metabolism and Regulation of Zhejiang Province, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, 310018, China
| | - Hongfa Li
- Hanguang Primary Processing Co., Ltd, Hangzhou, 311700, China
| | - Zhuoni Hou
- Key Laboratory of Plant Secondary Metabolism and Regulation of Zhejiang Province, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, 310018, China
| | - Zongsuo Liang
- Key Laboratory of Plant Secondary Metabolism and Regulation of Zhejiang Province, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, 310018, China
| |
Collapse
|
|
7
|
Harper P. A Review of the Dietary Intake, Bioavailability and Health Benefits of Ellagic Acid (EA) with a Primary Focus on Its Anti-Cancer Properties. Cureus 2023; 15:e43156. [PMID: 37692691 PMCID: PMC10484468 DOI: 10.7759/cureus.43156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/08/2023] [Indexed: 09/12/2023] Open
Abstract
Ellagitannins (ET) and ellagic acid (EA) are polyphenols, present in common foods, which may exhibit significant health benefits against inflammation, infection and cancer. EA is metabolised by the gut flora to produce urolithins, which are absorbed into the systemic circulation. Urolithins are widely documented to reduce oxidative stress associated with many diseases including cancer, heart disease and liver damage. In particular, Urolithin C and D have been shown to have high anti-oxidant properties through the inhibition of reactive oxygen species (ROS). The anti-inflammatory properties of EA have been demonstrated through the down-regulation of pro-inflammatory enzymes such as COX-2 and iNOS as well as decreasing the expression of adhesion molecules. EA also regulates the gut microflora and possesses antimicrobial activity against various strains of harmful bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) and Helicobacter pylori. Numerous studies have documented the anticarcinogenic benefits of EA and have been performed on, but not limited to, prostate, colon and breast cancer cell lines and in vivo models. Conventional treatments for cancer, such as chemotherapy, can often be associated with significant side effects such as fatigue, hair loss and alopecia. Naturally-occurring food substances such as ETs potentially offer a risk-free preventative measure against cancer and could perhaps be used in synergy with current treatments. More level 1 studies are required to inform the evidence-base on this topic.
Collapse
Affiliation(s)
- Philip Harper
- Life Sciences, University of Southampton, Southampton, GBR
| |
Collapse
|
|
8
|
Das G, Nath R, Das Talukdar A, Ağagündüz D, Yilmaz B, Capasso R, Shin HS, Patra JK. Major Bioactive Compounds from Java Plum Seeds: An Investigation of Its Extraction Procedures and Clinical Effects. PLANTS (BASEL, SWITZERLAND) 2023; 12:1214. [PMID: 36986906 PMCID: PMC10057433 DOI: 10.3390/plants12061214] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 03/02/2023] [Accepted: 03/03/2023] [Indexed: 06/18/2023]
Abstract
Java plum is widely recognized as a plant with valuable medicinal properties, originating from Indonesia and India and distributed globally in the tropic and sub-tropic regions of the world. The plant is rich in alkaloids, flavonoids, phenyl propanoids, terpenes, tannins, and lipids. The phytoconstituents of the plant seeds possess various vital pharmacological activities and clinical effects including their antidiabetic potential. The bioactive phytoconstituents of Java plum seeds include jambosine, gallic acid, quercetin, β-sitosterol, ferulic acid, guaiacol, resorcinol, p-coumaric acid, corilagin, ellagic acid, catechin, epicatechin, tannic acid, 4,6 hexahydroxydiphenoyl glucose, 3,6-hexahydroxy diphenoylglucose, 1-galloylglucose, and 3-galloylglucose. Considering all the potential beneficial effects of the major bioactive compounds present in the Jamun seeds, in the current investigation, the specific clinical effects and the mechanism of action for the major bioactive compounds along with the extraction procedures are discussed.
Collapse
Affiliation(s)
- Gitishree Das
- Research Institute of Integrative Life Sciences, Dongguk University-Seoul, Goyang-si 10326, Republic of Korea
| | - Rajat Nath
- Department of Life Science and Bioinformatics, Assam University, Silchar 788011, Assam, India
| | - Anupam Das Talukdar
- Department of Life Science and Bioinformatics, Assam University, Silchar 788011, Assam, India
| | - Duygu Ağagündüz
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Gazi University, Emek, Ankara 06490, Turkey
| | - Birsen Yilmaz
- Department of Biological Sciences, Tata Institute of Fundamental Research, Hyderabad 500046, Telangana, India
| | - Raffaele Capasso
- Department of Agricultural Sciences, University of Naples Federico II, 80138 Naples, Italy
| | - Han-Seung Shin
- Department of Food Science & Biotechnology, Dongguk University-Seoul, Goyang-si 10326, Republic of Korea
| | - Jayanta Kumar Patra
- Research Institute of Integrative Life Sciences, Dongguk University-Seoul, Goyang-si 10326, Republic of Korea
| |
Collapse
|
|
9
|
Pandey H, Tang DWT, Wong SH, Lal D. Gut Microbiota in Colorectal Cancer: Biological Role and Therapeutic Opportunities. Cancers (Basel) 2023; 15:cancers15030866. [PMID: 36765824 PMCID: PMC9913759 DOI: 10.3390/cancers15030866] [Citation(s) in RCA: 64] [Impact Index Per Article: 32.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Revised: 01/23/2023] [Accepted: 01/24/2023] [Indexed: 02/03/2023] Open
Abstract
Colorectal cancer (CRC) is the second-leading cause of cancer-related deaths worldwide. While CRC is thought to be an interplay between genetic and environmental factors, several lines of evidence suggest the involvement of gut microbiota in promoting inflammation and tumor progression. Gut microbiota refer to the ~40 trillion microorganisms that inhabit the human gut. Advances in next-generation sequencing technologies and metagenomics have provided new insights into the gut microbial ecology and have helped in linking gut microbiota to CRC. Many studies carried out in humans and animal models have emphasized the role of certain gut bacteria, such as Fusobacterium nucleatum, enterotoxigenic Bacteroides fragilis, and colibactin-producing Escherichia coli, in the onset and progression of CRC. Metagenomic studies have opened up new avenues for the application of gut microbiota in the diagnosis, prevention, and treatment of CRC. This review article summarizes the role of gut microbiota in CRC development and its use as a biomarker to predict the disease and its potential therapeutic applications.
Collapse
Affiliation(s)
- Himani Pandey
- Redcliffe Labs, Electronic City, Noida 201301, India
| | - Daryl W. T. Tang
- School of Biological Sciences, Nanyang Technological University, Singapore 308232, Singapore
| | - Sunny H. Wong
- Centre for Microbiome Medicine, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore
- Correspondence: (S.H.W.); (D.L.)
| | - Devi Lal
- Department of Zoology, Ramjas College, University of Delhi, Delhi 110007, India
- Correspondence: (S.H.W.); (D.L.)
| |
Collapse
|
|
10
|
Mohammadi M, Boghrati Z, Emami SA, Akaberi M. Pomegranate: A review of the heavenly healer's past, present, and future. IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES 2023; 26:1245-1264. [PMID: 37886004 PMCID: PMC10598818 DOI: 10.22038/ijbms.2023.72816.15844] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Subscribe] [Scholar Register] [Received: 06/04/2023] [Accepted: 07/15/2023] [Indexed: 10/28/2023]
Abstract
In the great Persian Empire, pomegranate (Punica granatum L.) had a wide reputation for use both as an herbal medicine and nutritious food. It was also a symbol of peace and love according to Achaemenid limestones in the great Persia. This paper aims to review the traditional uses of pomegranate in Persian and Islamic traditional medicine and have thorough and current information regarding the pharmacology and phytochemistry of this valuable plant for practical use and further research. Relevant information about P. granatum was collected from scientific publishers and databases including Elsevier, Wiley, PubMed, and Google Scholar between 1950 and 2022. The traditional knowledge was extracted from Persian and Islamic traditional textbooks. Based on traditional textbooks, pomegranate has beneficial effects on diseases related to gastrointestinal, upper and lower respiratory, visual, and reproductive systems. In addition, pomegranate and its preparations have been prescribed for treating metabolic disorders, skin problems, and wounds as well as dental protection. Preclinical and clinical evidence supports many therapeutic potentials of pomegranate in traditional medicine. Its therapeutic effects are mostly attributed to its polyphenols. The knowledge in Persian and Islamic traditional textbooks about pomegranate and its preparations can be used as a guide for further preclinical and mainly clinical studies to discover the therapeutic potential of this valuable plant.
Collapse
Affiliation(s)
- Mehran Mohammadi
- Department of Pharmacognosy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Zahra Boghrati
- Department of Traditional Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Seyed Ahmad Emami
- Department of Traditional Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Maryam Akaberi
- Department of Pharmacognosy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| |
Collapse
|
|
11
|
Zhang Y, Jiang L, Su P, Yu T, Ma Z, Liu Y, Yu J. Urolithin A suppresses tumor progression and induces autophagy in gastric cancer via the PI3K/Akt/mTOR pathway. Drug Dev Res 2022; 84:172-184. [PMID: 36477869 DOI: 10.1002/ddr.22021] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2022] [Revised: 11/01/2022] [Accepted: 11/18/2022] [Indexed: 12/12/2022]
Abstract
Urolithin A (UA) is a microbial metabolite of natural polyphenols ellagitannins and ellagic acid with well-established antitumor properties against various malignancies. However, the exact role of UA in gastric cancer (GC) progression remains largely unclear. In the present study, we investigated the effects and potential mechanisms of UA in GC in vitro and in vivo. Our results revealed that UA could suppress GC cell proliferation, inhibit migration and invasion, promote apoptosis, and induce autophagy via the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin pathway in vitro. The autophagy inhibitors 3-methyladenine and chloroquine augmented the inhibitory effect of UA on proliferation and promoted apoptosis, implying that UA mediated the cytoprotective role of autophagy. Meanwhile, the in vivo experiments showed that UA effectively suppressed tumor growth, enhanced the therapeutic effects, and alleviated chemotherapy toxicity in xenograft models. Overall, these findings offer novel insights into the role of UA in tumor therapy and suggest that UA may possess potential therapeutic applications for GC.
Collapse
Affiliation(s)
- Yingjing Zhang
- Department of General Surgery Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China
| | - Lin Jiang
- Department of General Surgery Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China
| | - Pengfei Su
- Department of General Surgery Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China
| | - Tian Yu
- Department of General Surgery Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China
| | - Zhiqiang Ma
- Department of General Surgery Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China
| | - Yuqin Liu
- Department of Pathology Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China
| | - Jianchun Yu
- Department of General Surgery Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China
| |
Collapse
|
|
12
|
Yang Y, Ren ZZ, Wei WJ, He ZL, Deng YL, Wang Z, Fan YC, Zhou J, Jiang LH. Study on the biological mechanism of urolithin a on nasopharyngeal carcinoma in vitro. PHARMACEUTICAL BIOLOGY 2022; 60:1566-1577. [PMID: 35952389 PMCID: PMC9377270 DOI: 10.1080/13880209.2022.2106251] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Revised: 06/08/2022] [Accepted: 07/22/2022] [Indexed: 06/15/2023]
Abstract
CONTEXT Urolithin A (UroA) can inhibit the growth of many human cancer cells, but it has not be reported if UroA inhibits nasopharyngeal carcinoma (NPC) cells. OBJECTIVE To explore the inhibitory effect of UroA on NPC and potential mechanism in vitro. MATERIALS AND METHODS RNA-sequencing-based mechanistic prediction was conducted by comparing KEGG enrichment of 40 μM UroA-treated for 24 h with untreated CNE2 cells. The untreated cells were selected as control. After NPC cells were treated with 20-60 μM UroA, proliferation, migration and invasion of were measured by colony formation, wound healing and transwell experiments. Apoptosis, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) were measured by flow cytometry, Hoechst 33342, Rhodamine 123, JC-1 staining and ROS assay methods, respectively. Gene and protein expression were measured by RT-qPCR and Western blotting assay. RESULTS RNA-sequencing and KEGG enrichment revealed UroA mainly altered the ECM receptor interaction pathway. UroA inhibited cells proliferation, epithelial-mesenchymal-transition pathway, migration and invasion with IC50 values of 34.72 μM and 44.91 μM, induced apoptosis, MMP depolarization and increase ROS content at a concentration of 40 μM. UroA up-regulated E-cadherin, Bax/Bcl-2, c-caspase-3 and PARP proteins, while inhibiting COL4A1, MMP2, MMP9, N-cadherin, Vimentin and Snail proteins at 20-60 μM. Moreover, co-treatment of UroA (40 μM) and NAC (5 mM) could reverse the effect of UroA on apoptosis-related proteins. DISCUSSION AND CONCLUSIONS RNA-sequencing technology based on bioinformatic analyses may be applicable for studiying the mechanism of drugs for tumour treatment.
Collapse
Affiliation(s)
- Yang Yang
- School of Pharmacy, Guilin Medical University, Guilin, PR China
- School of Basic Medical Sciences, Youjiang Medical University for Nationalities, Baise, PR China
| | - Zhen-Zhen Ren
- School of Pharmacy, Guilin Medical University, Guilin, PR China
- School of Basic Medical Sciences, Youjiang Medical University for Nationalities, Baise, PR China
| | - Wu-Jun Wei
- School of Basic Medical Sciences, Youjiang Medical University for Nationalities, Baise, PR China
- Department of Laboratory Medicine, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, PR China
| | - Zhi-Long He
- School of Basic Medical Sciences, Youjiang Medical University for Nationalities, Baise, PR China
- College of Light Industry and Food Engineering, Guangxi University, Nanning, PR China
| | - You-Lin Deng
- School of Basic Medical Sciences, Youjiang Medical University for Nationalities, Baise, PR China
| | - Zhuan Wang
- College of Light Industry and Food Engineering, Guangxi University, Nanning, PR China
| | - Yu-Chun Fan
- Medical College, Guangxi University, Nanning, PR China
| | - Jie Zhou
- Medical College, Guangxi University, Nanning, PR China
| | - Li-He Jiang
- School of Basic Medical Sciences, Youjiang Medical University for Nationalities, Baise, PR China
- College of Light Industry and Food Engineering, Guangxi University, Nanning, PR China
- Medical College, Guangxi University, Nanning, PR China
- Key Laboratory of Tumor Immunology and Pathology (Army Medical University), Ministry of Education, Chongqing, PR China
| |
Collapse
|
|
13
|
Mohammadinejad A, Mohajeri T, Aleyaghoob G, Heidarian F, Kazemi Oskuee R. Ellagic acid as a potent anticancer drug: A comprehensive review on in vitro, in vivo, in silico, and drug delivery studies. Biotechnol Appl Biochem 2022; 69:2323-2356. [PMID: 34846078 DOI: 10.1002/bab.2288] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Accepted: 11/10/2021] [Indexed: 12/27/2022]
Abstract
Ellagic acid as a polyphenol or micronutrient, which can be naturally found in different vegetables and fruits, has gained considerable attention for cancer therapy due to considerable biological activities and different molecular targets. Ellagic acid with low hydrolysis and lipophilic and hydrophobic nature is not able to be absorbed in circulation. So, accumulation inside the intestinal epithelial cells or metabolization to other urolithins leads to the limitation of direct evaluation of EA effects in clinical studies. This review focuses on the studies which supported anticancer activity of pure or fruit-extracted ellagic acid through in vitro, in vivo, in silico, and drug delivery methods. The results demonstrate ellagic acid modulates the expression of various genes incorporated in the cancer-related process of apoptosis and proliferation, inflammation related-gens, and oxidative-related genes. Moreover, the ellagic acid formulation in carriers composed of lipid, silica, chitosan, iron- bovine serum albumin nanoparticles obviously enhanced the stable release and confident delivery with minimum loss. Also, in silico analysis proved that ellagic acid was able to be placed at a position of cocrystal ADP, in the deep cavity of the protein target, and tightly interact with binding pocket residues leading to suppression of substrate availability of protein and its activation inhibition.
Collapse
Affiliation(s)
- Arash Mohammadinejad
- Targeted Drug Delivery Research Center, Institute of Pharmaceutical Technology, Mashhad University of Medical Sciences, Mashhad, Iran.,Department of Medical Biotechnology and Nanotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Taraneh Mohajeri
- Department of Obstetrics & Gynecology, Mashhad Medical Sciences Branch, Islamic Azad University, Mashhad, Iran
| | - Ghazaleh Aleyaghoob
- Department of Medical Biotechnology and Nanotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Fatemeh Heidarian
- Department of Medical Biotechnology and Nanotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Reza Kazemi Oskuee
- Department of Medical Biotechnology and Nanotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.,Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| |
Collapse
|
|
14
|
Tak Y, Kaur M, Jain MC, Samota MK, Meena NK, Kaur G, Kumar R, Sharma D, Lorenzo JM, Amarowicz R. Jamun Seed: A Review on Bioactive Constituents, Nutritional Value and Health Benefits. POL J FOOD NUTR SCI 2022. [DOI: 10.31883/pjfns/152568] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
|
|
15
|
Gandhi GR, Antony PJ, Ceasar SA, Vasconcelos ABS, Montalvão MM, Farias de Franca MN, Resende ADS, Sharanya CS, Liu Y, Hariharan G, Gan RY. Health functions and related molecular mechanisms of ellagitannin-derived urolithins. Crit Rev Food Sci Nutr 2022; 64:280-310. [PMID: 35959701 DOI: 10.1080/10408398.2022.2106179] [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] [Indexed: 11/03/2022]
Abstract
Ellagitannins are vital bioactive polyphenols that are widely distributed in a variety of plant-based foods. The main metabolites of ellagitannins are urolithins, and current research suggests that urolithins provide a variety of health benefits. This review focused on the role of the gut bacteria in the conversion of ellagitannins to urolithins. Based on the results of in vitro and in vivo studies, the health benefits of urolithins, including antioxidant, anti-inflammatory, anti-cancer, anti-obesity, anti-diabetic, anti-aging, cardiovascular protective, neuroprotective, kidney protective, and muscle mass protective effects, were thoroughly outlined, with a focus on their associated molecular mechanisms. Finally, we briefly commented on urolithins' safety. Overall, urolithins' diverse health benefits indicate the potential utilization of ellagitannins and urolithins in the creation of functional foods and nutraceuticals to treat and prevent some chronic diseases.
Collapse
Affiliation(s)
- Gopalsamy Rajiv Gandhi
- Department of Biosciences, Rajagiri College of Social Sciences, Kalamaserry, Kochi, India
| | | | | | - Alan Bruno Silva Vasconcelos
- Postgraduate Program of Physiological Sciences (PROCFIS), Federal University of Sergipe (UFS), São Cristóvão, Sergipe, Brazil
| | - Monalisa Martins Montalvão
- Postgraduate Program of Physiological Sciences (PROCFIS), Federal University of Sergipe (UFS), São Cristóvão, Sergipe, Brazil
| | - Mariana Nobre Farias de Franca
- Postgraduate Program of Health Sciences (PPGCS), Federal University of Sergipe (UFS), Campus Prof. João Cardoso Nascimento, Aracaju, CEP, Sergipe, Brazil
| | - Ayane de Sá Resende
- Postgraduate Program of Health Sciences (PPGCS), Federal University of Sergipe (UFS), Campus Prof. João Cardoso Nascimento, Aracaju, CEP, Sergipe, Brazil
| | | | - Yi Liu
- Research Center for Plants and Human Health, Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences (CAAS), Chengdu National Agricultural Science and Technology Center, Chengdu, China
| | - Govindasamy Hariharan
- Department of Biochemistry, Srimad Andavan Arts and Science College (Autonomous) affiliated to the Bharathidasan University, Tiruchirapalli, India
| | - Ren-You Gan
- Nepal Jesuit Society, St. Xavier's College, Jawalakhel, Lalitpur Dt. Kathmandu, Nepal
| |
Collapse
|
|
16
|
Wang X, Kahraman O, Feng H. Impact of Osmotic Dehydration With/Without Vacuum Pretreatment on Apple Slices Fortified With Hypertonic Fruit Juices. FOOD BIOPROCESS TECH 2022. [DOI: 10.1007/s11947-022-02834-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
|
|
17
|
Prabhakar P, Pavankumar GS, Raghu SV, Rao S, Prasad K, George T, Baliga MS. Utility of Indian fruits in cancer prevention and treatment: Time to undertake translational and bedside studies. Curr Pharm Des 2022; 28:1543-1560. [PMID: 35652402 DOI: 10.2174/1381612828666220601151931] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Accepted: 03/31/2022] [Indexed: 11/22/2022]
Abstract
The World Health Organization predicts a 70% increase in cancer incidents in developing nations over the next decade, and it will be the second leading cause of death worldwide. Traditional plant-based medicine systems play an important role against various diseases and provide health care to a large section of the population in developing countries. Indigenous fruits and their bioactive compounds with beneficial effects like antioxidant, antiproliferative, and immunomodulatory are shown to be useful in preventing the incidence of cancer. India is one of the biodiversity regions and is native to numerous flora and fauna in the world. Of the many fruiting trees indigenous to India, Mango (Mangifera indica), Black plum (Eugenia jambolana or Syzygium jambolana), Indian gooseberry (Emblica officinalis or Phyllanthus emblica), kokum (Garcinia indica or Brindonia indica), stone apple or bael (Aegle marmelos), Jackfruit (Artocarpus heterophyllus), Karaunda (Carissa carandas) and Phalsa (Grewia asiatica), Monkey Jackfruit (Artocarpus lakoocha) and Elephant apple (Dillenia indica) have been shown to be beneficial in preventing cancer and in the treatment of cancer in validated preclinical models of study. In this review, efforts are also made to collate the fruits' anticancer effects and the important phytochemicals. Efforts are also made at emphasizing the underlying mechanism/s responsible for the beneficial effects in cancer prevention and treatment. These fruits have been a part of the diet, are non-toxic, and easily acceptable for human application. The plants and some of their phytochemicals possess diverse medicinal properties. The authors propose that future studies should be directed at detailed studies with various preclinical models of study with both composite fruit extract/juice and the individual phytochemicals. Additionally, translational studies should be planned with the highly beneficial, well-investigated and pharmacologically multifactorial amla to understand its usefulness as a cancer preventive in the high-risk population and as a supportive agent in cancer survivors. The outcome of both preclinical and clinical studies will be useful for patients, the healthcare fraternity, pharmaceutical, and agro-based sectors.
Collapse
Affiliation(s)
- Pankaj Prabhakar
- Department of Pharmacology, Indira Gandhi Institute of Medical Sciences (IGIMS), Sheikhpura, Patna, Bihar, 800014, India
| | - Giriyapura Srikantachar Pavankumar
- Department of Biotechnology, Kuvempu University, India.,Sri Lakshmi Group of Institution, Magadi Main Road, Sunkadakatte, Bengaluru, Karnataka, India
| | - Shamprasad Varija Raghu
- Department of Applied Zoology, Mangalore University, Mangalagangotri, Konaje, Karnataka India
| | - Suresh Rao
- Radiation Oncology, c Pumpwell, Mangalore, Karnataka, India
| | - Krishna Prasad
- Medical Oncology, Mangalore Institute of Oncology, Pumpwell, Mangalore, Karnataka, India
| | - Thomas George
- Research Unit, Mangalore Institute of Oncology, Pumpwell, Mangalore, Karnataka, India
| | | |
Collapse
|
|
18
|
Interaction of Gut Microbiota with Endocrine Homeostasis and Thyroid Cancer. Cancers (Basel) 2022; 14:cancers14112656. [PMID: 35681636 PMCID: PMC9179244 DOI: 10.3390/cancers14112656] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Revised: 05/22/2022] [Accepted: 05/24/2022] [Indexed: 01/27/2023] Open
Abstract
The gut microbiota plays a crucial role in healthy individuals as well as in patients with thyroid diseases, including thyroid cancer. Although the prognosis of differentiated thyroid cancer is predictable, that of some poorly differentiated, medullary, and anaplastic thyroid cancers remains unpromising. As the interaction between the gut microbiota and thyroid cancer has been gradually revealed in recent years, the thyroid gland, a crucial endocrine organ, is shown to have a complex connection with the body's metabolism and is involved in inflammation, autoimmunity, or cancer progression. Dysbiosis of the gut microbiota and its metabolites can influence changes in hormone levels and susceptibility to thyroid cancer through multiple pathways. In this review, we focus on the interactions of the gut microbiota with thyroid function diseases and thyroid cancer. In addition, we also discuss some potential new strategies for the prevention and treatment of thyroid disease and thyroid cancer. Our aim is to provide some possible clinical applications of gut microbiota markers for early diagnosis, treatment, and postoperative management of thyroid cancer. These findings were used to establish a better multi-disciplinary treatment and prevention management strategy and to individualize the treatment of patients in relation to their gut microbiota composition and pathological characteristics.
Collapse
|
|
19
|
Kamal N, Ilowefah MA, Hilles AR, Anua NA, Awin T, Alshwyeh HA, Aldosary SK, Jambocus NGS, Alosaimi AA, Rahman A, Mahmood S, Mediani A. Genesis and Mechanism of Some Cancer Types and an Overview on the Role of Diet and Nutrition in Cancer Prevention. Molecules 2022; 27:1794. [PMID: 35335158 PMCID: PMC8955916 DOI: 10.3390/molecules27061794] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2022] [Revised: 02/28/2022] [Accepted: 03/07/2022] [Indexed: 02/01/2023] Open
Abstract
Cancer is a major disease with a high mortality rate worldwide. In many countries, cancer is considered to be the second most common cause of death after cardiovascular disease. The clinical management of cancer continues to be a challenge as conventional treatments, such as chemotherapy and radiation therapy, have limitations due to their toxicity profiles. Unhealthy lifestyle and poor dietary habits are the key risk factors for cancer; having a healthy diet and lifestyle may minimize the risk. Epidemiological studies have shown that a high fruit and vegetable intake in our regular diet can effectively reduce the risk of developing certain types of cancers due to the high contents of antioxidants and phytochemicals. In vitro and in vivo studies have shown that phytochemicals exert significant anticancer effects due to their free radical scavenging capacity potential. There has been extensive research on the protective effects of phytochemicals in different types of cancers. This review attempts to give an overview of the etiology of different types of cancers and assesses the role of phytonutrients in the prevention of cancers, which makes the present review distinct from the others available.
Collapse
Affiliation(s)
- Nurkhalida Kamal
- Institute of Systems Biology, Universiti Kebangsaan Malaysia (UKM), Bangi 43600, Malaysia; (N.K.); (N.A.A.)
| | - Muna Abdulsalam Ilowefah
- Department of Food Technology, Faculty of Engineering and Technology, Sabha University, Sabha 00218, Libya;
| | - Ayah Rebhi Hilles
- Institute for Halal Research and Training (INHART), International Islamic University Malaysia, Kuala Lumpur 53100, Malaysia;
| | - Nurul Adlina Anua
- Institute of Systems Biology, Universiti Kebangsaan Malaysia (UKM), Bangi 43600, Malaysia; (N.K.); (N.A.A.)
| | - Tahani Awin
- Department of Chemistry, Faculty of Science, University of Benghazi, Qar Yunis, Benghazi 5341, Libya;
| | - Hussah Abdullah Alshwyeh
- Department of Biology, College of Science, Imam Abdulrahman Bin Faisal University, Dammam 34212, Saudi Arabia; (H.A.A.); (S.K.A.); (A.A.A.)
- Basic & Applied Scientific Research Centre, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia
| | - Sahar Khamees Aldosary
- Department of Biology, College of Science, Imam Abdulrahman Bin Faisal University, Dammam 34212, Saudi Arabia; (H.A.A.); (S.K.A.); (A.A.A.)
| | - Najla Gooda Sahib Jambocus
- Ministry of Education, Tertiary Education, Science and Technology, MITD House, Phoenix 73544, Mauritius;
| | - Areej A. Alosaimi
- Department of Biology, College of Science, Imam Abdulrahman Bin Faisal University, Dammam 34212, Saudi Arabia; (H.A.A.); (S.K.A.); (A.A.A.)
| | - Azizur Rahman
- Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, UCSI University, Kuala Lumpur 56000, Malaysia;
| | - Syed Mahmood
- Department of Pharmaceutical Technology, Faculty of Pharmacy, Universiti Malaya, Kuala Lumpur 50603, Malaysia
| | - Ahmed Mediani
- Institute of Systems Biology, Universiti Kebangsaan Malaysia (UKM), Bangi 43600, Malaysia; (N.K.); (N.A.A.)
| |
Collapse
|
|
20
|
Kombiyil S, Sivasithamparam ND. In Vitro Anti-cancer Effect of Crataegus oxyacantha Berry Extract on Hormone Receptor Positive and Triple Negative Breast Cancers via Regulation of Canonical Wnt Signaling Pathway. Appl Biochem Biotechnol 2022; 195:2687-2708. [PMID: 35262883 DOI: 10.1007/s12010-021-03724-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Accepted: 10/08/2021] [Indexed: 11/29/2022]
Abstract
Breast cancer treatment strategy depends mainly on the receptor status. Our aim was to identify a herbal preparation, effective against breast cancer, irrespective of hormone sensitivity, and to understand its molecular mechanism. The rich antioxidant composition of hawthorn (Crataegus oxyacantha) makes it a promising anti-cancer drug candidate. Polyphenol-rich methanolic extract of C. oxyacantha berry (M.Co) was found to be cytotoxic on hormone receptor positive (MCF-7) and triple negative (MDA-MB-231) breast cancer cell lines, at a dose (75 μg/ml) safe on normal cells. It could effectively inhibit tumor cell proliferation and arrest cell cycle at G1/S transition in both cell lines. Molecular targets were selected from different levels of canonical Wnt signaling pathway (such as autocrine and antagonistic ligands, receptor, effector, cytoplasmic components, downstream targets, and pathway antagonist), since they are frequently found dysregulated in all breast cancers and their aberrant activation is associated with cancer stem cell expansion. M.Co could significantly downregulate the expression of Wnt pathway agonists and upregulate that of Wnt antagonists at transcriptional and translational levels, in both cell lines. To conclude, C. oxyacantha berry extract is effective against breast cancer irrespective of its hormone dependency, and cancer growth inhibition at stem cell level can be expected.
Collapse
Affiliation(s)
- Salini Kombiyil
- Department of Biochemistry, University of Madras, Guindy Campus, Chennai, 600025, India
| | | |
Collapse
|
|
21
|
Zhang M, Cui S, Mao B, Zhang Q, Zhao J, Zhang H, Tang X, Chen W. Ellagic acid and intestinal microflora metabolite urolithin A: A review on its sources, metabolic distribution, health benefits, and biotransformation. Crit Rev Food Sci Nutr 2022; 63:6900-6922. [PMID: 35142569 DOI: 10.1080/10408398.2022.2036693] [Citation(s) in RCA: 53] [Impact Index Per Article: 17.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Foods rich in ellagic tannins are first hydrolyzed into ellagic acid in the stomach and small intestine, and then converted into urolithins with high bioavailability by the intestinal flora. Urolithin has beneficially biological effects, it can induce adipocyte browning, improve cholesterol metabolism, inhibit graft tumor growth, relieve inflammation, and downregulate neuronal amyloid protein formation via the β3-AR/PKA/p38MAPK, ERK/AMPKα/SREBP1, PI3K/AKT/mTOR signaling pathways, and TLR4, AHR receptors. But differences have been reported in urolithin production capacity among different individuals. Thus, it is of great significance to explore the biological functions of urolithin, screen the strains responsible for biotransformation of urolithin, and explore the corresponding functional genes. Tannin acyl hydrolase can hydrolyze tannins into ellagic acid, and the genera Gordonibacter and Ellagibacter can metabolize ellagic acid into urolithins. Therefore, application of "single bacterium", "single bacterium + enzyme", and "microflora" can achieve biotransformation of urolithin A. In this review, the source and metabolic pathway of ellagic tannins, and the mechanisms of the biological function of a metabolite, urolithin A, are discussed. The current strategies of biotransformation to obtain urolithin A are expounded to provide ideas for further studies on the relationship between urolithin and human health.
Collapse
Affiliation(s)
- Mengwei Zhang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, P. R China
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, P. R China
| | - Shumao Cui
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, P. R China
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, P. R China
| | - Bingyong Mao
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, P. R China
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, P. R China
| | - Qiuxiang Zhang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, P. R China
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, P. R China
| | - Jianxin Zhao
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, P. R China
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, P. R China
| | - Hao Zhang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, P. R China
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, P. R China
- National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, Jiangsu, P. R China
- Wuxi Translational Medicine Research Center, Jiangsu Translational Medicine Research Institute Wuxi Branch, Wuxi, Jiangsu, P. R China
| | - Xin Tang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, P. R China
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, P. R China
| | - Wei Chen
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, P. R China
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, P. R China
- National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, Jiangsu, P. R China
| |
Collapse
|
|
22
|
Moreno RU, Gonzalez-Sarrias A, Espin JC, Tomas-Barberan F, Janes ME, Cheng H, Finley JW, Greenway FL, Losso JN. Effects of red raspberry polyphenols and metabolites on biomarkers of inflammation and insulin resistance in type 2 diabetes: A pilot study. Food Funct 2022; 13:5166-5176. [DOI: 10.1039/d1fo02090k] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Berry fruits are rich in polyphenolic compounds (PCs) and may promote health benefits. Anthocyanin (ACNs) concentrations of red raspberry (RR)(Rubus idaeus) extracts were 887.6 ± 262.8 μg/g consisting mainly of...
Collapse
|
|
23
|
Tang L, Jiang J, Song G, Wang Y, Zhuang Z, Tan Y, Xia Y, Huang X, Feng X. Design, synthesis, and biological evaluation of novel urolithins derivatives as potential phosphodiesterase II inhibitors. Sci Rep 2021; 11:23792. [PMID: 34893678 PMCID: PMC8664850 DOI: 10.1038/s41598-021-03194-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Accepted: 11/16/2021] [Indexed: 11/09/2022] Open
Abstract
A series of urolithins derivatives were designed and synthesized, and their structures have been confirmed by 1H NMR, 13C NMR, and HR-MS. The inhibitory activity of these derivatives on phosphodiesterase II (PDE2) was thoroughly studied with 3-hydroxy-8-methyl-6H-benzo[C]chromen-6-one and 3-hydroxy-7,8,9,10-tetrahydro-6H-benzo[C] chromen-6-one as the lead compounds. The biological activity test showed that compound 2e had the best inhibitory activity on PDE2 with an IC50 of 33.95 μM. This study provides a foundation for further structural modification and transformation of urolithins to obtain PDE2 inhibitor small molecules with better inhibitory activity.
Collapse
Affiliation(s)
- Long Tang
- Institute of Chemical Industry of Forest Products, Chinese Academy of Forestry, Nanjing, 210042, China.,School of Chemical Engineering, Nanjing Forestry University, Nanjing, 210037, China.,School of Pharmaceutical Engineering & Life Science, Changzhou University, Changzhou, 213164, China
| | - Jianchun Jiang
- Institute of Chemical Industry of Forest Products, Chinese Academy of Forestry, Nanjing, 210042, China.,School of Chemical Engineering, Nanjing Forestry University, Nanjing, 210037, China
| | - Guoqiang Song
- School of Pharmaceutical Engineering & Life Science, Changzhou University, Changzhou, 213164, China
| | - Yajing Wang
- School of Pharmaceutical Engineering & Life Science, Changzhou University, Changzhou, 213164, China
| | - Ziheng Zhuang
- School of Pharmaceutical Engineering & Life Science, Changzhou University, Changzhou, 213164, China
| | - Ying Tan
- School of Pharmaceutical Engineering & Life Science, Changzhou University, Changzhou, 213164, China
| | - Yan Xia
- School of Pharmaceutical Engineering & Life Science, Changzhou University, Changzhou, 213164, China
| | - Xianfeng Huang
- School of Pharmaceutical Engineering & Life Science, Changzhou University, Changzhou, 213164, China
| | - Xiaoqing Feng
- School of Pharmaceutical Engineering & Life Science, Changzhou University, Changzhou, 213164, China.
| |
Collapse
|
|
24
|
Hasheminezhad SH, Boozari M, Iranshahi M, Yazarlu O, Sahebkar A, Hasanpour M, Iranshahy M. A mechanistic insight into the biological activities of urolithins as gut microbial metabolites of ellagitannins. Phytother Res 2021; 36:112-146. [PMID: 34542202 DOI: 10.1002/ptr.7290] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Revised: 08/06/2021] [Accepted: 09/04/2021] [Indexed: 12/26/2022]
Abstract
Urolithins are the gut metabolites produced from ellagitannin-rich foods such as pomegranates, tea, walnuts, as well as strawberries, raspberries, blackberries, and cloudberries. Urolithins are of growing interest due to their various biological activities including cardiovascular protection, anti-inflammatory activity, anticancer properties, antidiabetic activity, and antiaging properties. Several studies mostly based on in vitro and in vivo experiments have investigated the potential mechanisms of urolithins which support the beneficial effects of urolithins in the treatment of several diseases such as Alzheimer's disease, type 2 diabetes mellitus, liver disease, cardiovascular disease, and various cancers. It is now obvious that urolithins can involve several cellular mechanisms including inhibition of MDM2-p53 interaction, modulation of mitogen-activated protein kinase pathway, and suppressing nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activity. Antiaging activity is the most appealing and probably the most important property of urolithin A that has been investigated in depth in recent studies, owing to its unique effects on activation of mitophagy and mitochondrial biogenesis. A recent clinical trial showed that urolithin A is safe up to 2,500 mg/day and can improve mitochondrial biomarkers in elderly patients. Regarding the importance of mitochondria in the pathophysiology of many diseases, urolithins merit further research especially in clinical trials to unravel more aspects of their clinical significance. Besides the nutritional value of urolithins, recent studies proved that urolithins can be used as pharmacological agents to prevent or cure several diseases. Here, we comprehensively review the potential role of urolithins as new therapeutic agents with a special focus on the molecular pathways that have been involved in their biological effects. The pharmacokinetics of urolithins is also included.
Collapse
Affiliation(s)
| | - Motahareh Boozari
- Department of Pharmacognosy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mehrdad Iranshahi
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Omid Yazarlu
- Department of General Surgery, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Maede Hasanpour
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Milad Iranshahy
- Department of Pharmacognosy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| |
Collapse
|
|
25
|
Park WY, Park J, Ahn KS, Kwak HJ, Um JY. Ellagic acid induces beige remodeling of white adipose tissue by controlling mitochondrial dynamics and SIRT3. FASEB J 2021; 35:e21548. [PMID: 33956354 DOI: 10.1096/fj.202002491r] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2020] [Revised: 02/25/2021] [Accepted: 03/08/2021] [Indexed: 12/16/2022]
Abstract
To determine whether ellagic acid (EA) induces the "beige remodeling" of white adipose tissue (WAT), we treated cold-exposed mice and mouse stromal vascular fraction (SVF) cells with EA, a phytochemical abundant in fruits and vegetables, in particular berries. We then investigated the mechanism of EA in beige remodeling with a particular focus on DRP1-mediated mitochondrial fission and SIRT3. EA induced the trans-differentiation of white adipocytes to beige adipocytes by promoting the expression of UCP1 and other brown and beige adipocytes/fat factors (PRDM16, UCP1, PGC1α, CD137, and TBX1) and mitochondrial dynamics-related factors (SIRT3, NRF1, CPT1β, DRP1, and FIS1) in 3T3-L1/SVF cells, and these were confirmed in the inguinal WAT of a cold-exposed mouse model. The browning effect of EA was abolished by a potent DRP1 inhibitor Mdivi-1 or SIRT3 knockdown, suggesting that EA induces beige remodeling of WAT by regulating the mitochondrial dynamics and SIRT3.
Collapse
Affiliation(s)
- Woo Yong Park
- Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul, Republic of Korea.,Basic Research Laboratory for Comorbidity Research and Comorbidity Research Institute, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
| | - Jinbong Park
- Basic Research Laboratory for Comorbidity Research and Comorbidity Research Institute, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.,Department of Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
| | - Kwang Seok Ahn
- Basic Research Laboratory for Comorbidity Research and Comorbidity Research Institute, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
| | - Hyun Jeong Kwak
- Department of Life Science, College of Natural Sciences, Kyonggi University, Suwon, Republic of Korea
| | - Jae-Young Um
- Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul, Republic of Korea.,Basic Research Laboratory for Comorbidity Research and Comorbidity Research Institute, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.,Department of Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
| |
Collapse
|
|
26
|
Al-Harbi SA, Abdulrahman AO, Zamzami MA, Khan MI. Urolithins: The Gut Based Polyphenol Metabolites of Ellagitannins in Cancer Prevention, a Review. Front Nutr 2021; 8:647582. [PMID: 34164422 PMCID: PMC8215145 DOI: 10.3389/fnut.2021.647582] [Citation(s) in RCA: 64] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Accepted: 04/28/2021] [Indexed: 12/17/2022] Open
Abstract
Cancer as a disease continues to ravage the world population without regard to sex, age, and race. Due to the growing number of cases worldwide, cancer exerts a significant negative impact on global health and the economy. Interestingly, chemotherapy has been used over the years as a therapeutic intervention against cancer. However, high cost, resistance, and toxic by-effects to treatment have overshadowed some of its benefits. In recent times, efforts have been ongoing in searching for anticancer therapeutics of plant origin, focusing on polyphenols. Urolithins are secondary polyphenol metabolites derived from the gut microbial action on ellagitannins and ellagic acid-rich foods such as pomegranate, berries, and nuts. Urolithins are emerging as a new class of anticancer compounds that can mediate their cancer-preventive activities through cell cycle arrest, aromatase inhibition, induction of apoptosis, tumor suppression, promotion of autophagy, and senescence, transcriptional regulation of oncogenes, and growth factor receptors. In this review, we discussed the growing shreds of evidence supporting these secondary phenolic metabolites' anticancer properties. Furthermore, we have pointed out some of the future directions needed to establish urolithins as anticancer agents.
Collapse
Affiliation(s)
- Sami A Al-Harbi
- Department of Chemistry, University College in Al-Jamoum, Umm Al-Qura University, Makkah, Saudi Arabia
| | | | - Mazin A Zamzami
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.,Cancer Metabolism and Epigenetic Unit, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Mohammad Imran Khan
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.,Cancer Metabolism and Epigenetic Unit, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia
| |
Collapse
|
|
27
|
Design, Synthesis, and Biological Evaluation of Novel 6 H-Benzo[ c]chromen-6-one Derivatives as Potential Phosphodiesterase II Inhibitors. Int J Mol Sci 2021; 22:ijms22115680. [PMID: 34073595 PMCID: PMC8199001 DOI: 10.3390/ijms22115680] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Revised: 05/21/2021] [Accepted: 05/25/2021] [Indexed: 11/17/2022] Open
Abstract
Urolithins (hydroxylated 6H-benzo[c]chromen-6-ones) are the main bioavailable metabolites of ellagic acid (EA), which was shown to be a cognitive enhancer in the treatment of neurodegenerative diseases. As part of this research, a series of alkoxylated 6H-benzo[c]chromen-6-one derivatives were designed and synthesized. Furthermore, their biological activities were evaluated as potential PDE2 inhibitors, and the alkoxylated 6H-benzo[c]chromen-6-one derivative 1f was found to have the optimal inhibitory potential (IC50: 3.67 ± 0.47 μM). It also exhibited comparable activity in comparison to that of BAY 60-7550 in vitro cell level studies.
Collapse
|
|
28
|
Pectin-Based Formulations for Controlled Release of an Ellagic Acid Salt with High Solubility Profile in Physiological Media. Molecules 2021; 26:molecules26020433. [PMID: 33467593 PMCID: PMC7829853 DOI: 10.3390/molecules26020433] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Revised: 12/28/2020] [Accepted: 01/13/2021] [Indexed: 01/08/2023] Open
Abstract
Among bioactive phytochemicals, ellagic acid (EA) is one of the most controversial because its high antioxidant and cancer-preventing effects are strongly inhibited by low gastrointestinal absorption and rapid excretion. Strategies toward an increase of solubility in water and bioavailability, while preserving its structural integrity and warranting its controlled release at the physiological targets, are therefore largely pursued. In this work, EA lysine salt at 1:4 molar ratio (EALYS), exhibiting a more than 400 times increase of water solubility with respect to literature reports, was incorporated at 10% in low methoxylated (LM) and high methoxylated (HM) pectin films. The release of EA in PBS at pH 7.4 from both film preparations was comparable and reached 15% of the loaded compound over 2 h. Under simulated gastric conditions, release of EA from HM and LM pectin films was minimal at gastric pH, whereas higher concentrations—up to 300 μM, corresponding to ca. 50% of the overall content—were obtained in the case of the HM pectin film after 2 h incubation at the slightly alkaline pH of small intestine environment, with the enzyme and bile salt components enhancing the release. EALYS pectin films showed a good prebiotic activity as evaluated by determination of short chain fatty acids (SCFAs) levels following microbial fermentation, with a low but significant increase of the effects produced by the pectins themselves. Overall, these results highlight pectin films loaded with EALYS salt as a promising formulation to improve administration and controlled release of the compound.
Collapse
|
|
29
|
Yi S, Zhang C, Hu J, Meng Y, Chen L, Yu H, Li S, Wang G, Zheng G, Qiu Z. Preparation, Characterization, and In Vitro Pharmacodynamics and Pharmacokinetics Evaluation of PEGylated Urolithin A Liposomes. AAPS PharmSciTech 2021; 22:26. [PMID: 33404864 DOI: 10.1208/s12249-020-01890-y] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Accepted: 11/27/2020] [Indexed: 12/27/2022] Open
Abstract
Urolithin A (Uro-A), a metabolite of ellagitannins in mammals' intestinal tract, displays broad biological properties in preclinical models, including anti-oxidant, anti-inflammatory, and anti-tumor effects. However, the clinical application of Uro-A is restricted because of its low aqueous solubility and short elimination half-life. Our purpose was to develop a delivery system to improve the bioavailability and anti-tumor efficacy of Uro-A. To achieve this goal, urolithin A-loaded PEGylated liposomes (Uro-A-PEG-LPs) were prepared for the first time and its physicochemical properties and anti-tumor efficacy in vitro were evaluated. The morphology of Uro-A-PEG-LPs displayed a uniform sphere under transmission electron microscope. The particle size, polydispersity index, zeta potential, and encapsulation efficiency of Uro-A-PEG-LPs were 122.8 ± 7.4 nm, 0.25 ± 0.16, - 25.5 ± 2.3 mV, and 94.6 ± 1.6%, respectively. Moreover, Uro-A-PEG-LPs possessed higher stability and could be stably stored at 4°C for a long time. In vitro release characteristics indicated that Uro-A-PEG-LPs possessed superior sustained release properties. The results of confocal laser scanning microscopy experiment showed that the coumarin 6-loaded PEGylated liposomes (C6-PEG-LPs) have superior cellular uptake than that of conventional liposomes. In addition, in vitro tests demonstrated that Uro-A-PEG-LPs elevated cytotoxicity and pro-apoptotic effect in human hepatoma cells comparing with free Uro-A. Furthermore, the results of pharmacokinetic experiments showed that the t1/2, AUC0-t, and MRT0-t of Uro-A-PEG-LPs increased to 4.58-fold, 2.33-fold, and 2.43-fold than those of free Uro-A solution, respectively. Collectively, these manifested that PEGylated liposomes might be a potential delivery system for Uro-A to prolonging in vivo circulation time, promoting cellular uptake, and enhancing its anti-tumor efficacy.
Collapse
|
|
30
|
Hayes PE, Glennon JD, Luong JHT. Electroanalysis of Gallic and Ellagic Acids at a Boron‐doped Diamond Electrode Coupled with High‐performance Liquid Chromatography. ELECTROANAL 2020. [DOI: 10.1002/elan.202060021] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Affiliation(s)
- Phyllis E. Hayes
- Innovative Chromatography Group, Irish Separation Science Cluster (ISSC), School of Chemistry and the Analytical & Biological Chemistry Research Facility (ABCRF) University College Cork College Road Cork T12 YN60 Ireland
| | - Jeremy D. Glennon
- Innovative Chromatography Group, Irish Separation Science Cluster (ISSC), School of Chemistry and the Analytical & Biological Chemistry Research Facility (ABCRF) University College Cork College Road Cork T12 YN60 Ireland
| | - John H. T. Luong
- Innovative Chromatography Group, Irish Separation Science Cluster (ISSC), School of Chemistry and the Analytical & Biological Chemistry Research Facility (ABCRF) University College Cork College Road Cork T12 YN60 Ireland
| |
Collapse
|
|
31
|
Noshadi B, Ercetin T, Luise C, Yuksel MY, Sippl W, Sahin MF, Gazi M, Gulcan HO. Synthesis, Characterization, Molecular Docking, and Biological Activities of Some Natural and Synthetic Urolithin Analogs. Chem Biodivers 2020; 17:e2000197. [PMID: 32497364 DOI: 10.1002/cbdv.202000197] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Accepted: 06/04/2020] [Indexed: 01/17/2023]
Abstract
Urolithins (that is, hydroxy substituted benzo[c]chromen-6-one derivatives) are formed within the gastrointestinal tract following to the exposure to various ellagitannin rich diet, particularly involving pomegranate, nuts, and berries. Regarding the bioavailability deficiency of ellagitannins, the biological activities obtained through the extracts of these dietaries are attributed to the urolithin compounds, since they are bioavailable. Particularly, there are studies indicating the importance of ellagitannin-rich food for protective and alternative treatment of Alzheimer's Disease (AD). From this perspective, within this study, the major urolithins (that is, urolithins A and B), their methyl ether metabolites, as well as some synthetic urolithin analogs have been synthesized and screened for their biological activities in various enzyme inhibition (acetylcholinesterase, butyrylcholinesterase, monoamine oxidase B, cyclooxygenase 1, and cyclooxygenase 2) and antioxidant (DPPH radical scavenging) assay systems. The results pointed out the potential of urolithins to act as inhibitors on these receptors. Docking studies were also performed to investigate the possible interactions.
Collapse
Affiliation(s)
- Bahareh Noshadi
- Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Eastern Mediterranean University, via Mersin 10, TR-99628, Famagusta, North Cyprus, Turkey.,Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Eastern Mediterranean University, via Mersin 10, TR-99628, Famagusta, North Cyprus, Turkey
| | - Tugba Ercetin
- Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Eastern Mediterranean University, via Mersin 10, TR-99628, Famagusta, North Cyprus, Turkey
| | - Chiara Luise
- Institute of Pharmacy, Martin Luther University of Halle-Wittenberg, Kurt-Mothes-Str.3, DE-06120, Halle/Saale, Germany
| | - Mine Yarim Yuksel
- Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Yeditepe University, TR-34755, Istanbul, Turkey
| | - Wolfgang Sippl
- Institute of Pharmacy, Martin Luther University of Halle-Wittenberg, Kurt-Mothes-Str.3, DE-06120, Halle/Saale, Germany
| | - Mustafa Fethi Sahin
- Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Eastern Mediterranean University, via Mersin 10, TR-99628, Famagusta, North Cyprus, Turkey
| | - Mustafa Gazi
- Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Eastern Mediterranean University, via Mersin 10, TR-99628, Famagusta, North Cyprus, Turkey
| | - Hayrettin Ozan Gulcan
- Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Eastern Mediterranean University, via Mersin 10, TR-99628, Famagusta, North Cyprus, Turkey
| |
Collapse
|
|
32
|
Kujawska M, Jodynis-Liebert J. Potential of the ellagic acid-derived gut microbiota metabolite - Urolithin A in gastrointestinal protection. World J Gastroenterol 2020; 26:3170-3181. [PMID: 32684733 PMCID: PMC7336321 DOI: 10.3748/wjg.v26.i23.3170] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Revised: 05/19/2020] [Accepted: 05/23/2020] [Indexed: 02/06/2023] Open
Abstract
Urolithin A (UA) is a metabolic compound generated during the biotransformation of ellagitannins by the intestinal bacteria. The physiologically relevant micromolar concentrations of UA, achieved in the plasma and gastrointestinal tract (GI) after consumption of its dietary precursors, have been revealed to offer GI protection. The health benefit has been demonstrated to be principally related to anticancer and anti-inflammatory effects. UA has been shown to possess the capability to regulate multiple tumor and inflammatory signaling pathways and to modulate enzyme activity, including those involved in carcinogen biotransformation and antioxidant defense. The purpose of this review is to gather evidence from both in vitro and in vivo studies showing the potential of UA in GI protection alongside suggested mechanisms by which UA can protect against cancer and inflammatory diseases of the digestive tract. The data presented herein, covering both studies on the pure compound and in vivo generated UA form its natural precursor, support the potential of this metabolite in treatment interventions against GI ailments.
Collapse
Affiliation(s)
- Małgorzata Kujawska
- Department of Toxicology, Poznan University of Medical Sciences, Poznan 60631, Poland
| | | |
Collapse
|
|
33
|
Loo YT, Howell K, Chan M, Zhang P, Ng K. Modulation of the human gut microbiota by phenolics and phenolic fiber-rich foods. Compr Rev Food Sci Food Saf 2020; 19:1268-1298. [PMID: 33337077 DOI: 10.1111/1541-4337.12563] [Citation(s) in RCA: 131] [Impact Index Per Article: 26.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2018] [Revised: 03/16/2020] [Accepted: 03/21/2020] [Indexed: 12/18/2022]
Abstract
The gut microbiota plays a prominent role in human health. Alterations in the gut microbiota are linked to the development of chronic diseases such as obesity, inflammatory bowel disease, metabolic syndrome, and certain cancers. We know that diet plays an important role to initiate, shape, and modulate the gut microbiota. Long-term dietary patterns are shown to be closely related with the gut microbiota enterotypes, specifically long-term consumption of carbohydrates (related to Prevotella abundance) or a diet rich in protein and animal fats (correlated to Bacteroides). Short-term consumption of solely animal- or plant-based diets have rapid and reproducible modulatory effects on the human gut microbiota. These alterations in microbiota profile by dietary alterations can be due to impact of different dietary macronutrients, carbohydrates, protein, and fat, which have diverse modulatory effects on gut microbial composition. Food-derived phenolics, which encompass structural variants of flavonoids, hydroxybenzoic acids, hydroxycinnamic acids, coumarins, stilbenes, ellagitannins, and lignans can modify the gut microbiota. Gut microbes have been shown to act on dietary fibers and phenolics to produce functional metabolites that contribute to gut health. Here, we discuss recent studies on the impacts of phenolics and phenolic fiber-rich foods on the human gut microbiota and provide an insight into potential synergistic roles between their bacterial metabolic products in the regulation of the intestinal microbiota.
Collapse
Affiliation(s)
- Yit Tao Loo
- School of Agriculture & Food, Faculty of Veterinary & Agricultural Sciences, The University of Melbourne, Melbourne, Victoria, Australia
| | - Kate Howell
- School of Agriculture & Food, Faculty of Veterinary & Agricultural Sciences, The University of Melbourne, Melbourne, Victoria, Australia
| | - Miin Chan
- School of Agriculture & Food, Faculty of Veterinary & Agricultural Sciences, The University of Melbourne, Melbourne, Victoria, Australia
| | - Pangzhen Zhang
- School of Agriculture & Food, Faculty of Veterinary & Agricultural Sciences, The University of Melbourne, Melbourne, Victoria, Australia
| | - Ken Ng
- School of Agriculture & Food, Faculty of Veterinary & Agricultural Sciences, The University of Melbourne, Melbourne, Victoria, Australia
| |
Collapse
|
|
34
|
Evaluation of electron-transferring cofactor mediating enzyme systems involved in urolithin dehydroxylation in Gordonibacter urolithinfaciens DSM 27213. J Biosci Bioeng 2020; 129:552-557. [DOI: 10.1016/j.jbiosc.2019.11.014] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2019] [Revised: 11/27/2019] [Accepted: 11/28/2019] [Indexed: 11/18/2022]
|
|
35
|
Vandana UK, Barlaskar NH, Gulzar ABM, Laskar IH, Kumar D, Paul P, Pandey P, Mazumder PB. Linking gut microbiota with the human diseases. Bioinformation 2020; 16:196-208. [PMID: 32405173 PMCID: PMC7196170 DOI: 10.6026/97320630016196] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2020] [Accepted: 02/20/2020] [Indexed: 12/13/2022] Open
Abstract
The human gut is rich in microbes. Therefore, it is of interest to document data to link known human diseases with the gut microbiota. Various factors like hormones, metabolites and dietary habitats are responsible for shaping the microbiota of the gut. Imbalance in the gut microbiota is responsible for the pathogenesis of various disease types including rheumatoid arthritis, different types of cancer, diabetes mellitus, obesity, and cardiovascular disease. We report a review of known data for the correction of dysbiosis (imbalance in microbe population) towards improved human health.
Collapse
Affiliation(s)
| | | | | | | | - Diwakar Kumar
- Department of Microbiology, Assam University, Silchar, Assam, India
| | - Prosenjit Paul
- Department of Biotechnology, Assam University, Silchar, Assam, India
| | - Piyush Pandey
- Department of Microbiology, Assam University, Silchar, Assam, India
| | | |
Collapse
|
|
36
|
Alauddin M, Okumura T, Rajaxavier J, Khozooei S, Pöschel S, Takeda S, Singh Y, Brucker SY, Wallwiener D, Koch A, Salker MS. Gut Bacterial Metabolite Urolithin A Decreases Actin Polymerization and Migration in Cancer Cells. Mol Nutr Food Res 2020; 64:e1900390. [PMID: 31976617 DOI: 10.1002/mnfr.201900390] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Revised: 12/11/2019] [Indexed: 12/12/2022]
Abstract
SCOPE Urolithin A (UA) is a gut-derived bacterial metabolite from ellagic acid found in pomegranates, berries, and nuts can downregulate cell proliferation and migration. Cell proliferation and cell motility require actin reorganization, which is under control of ras-related C3 botulinum toxin substrate 1 (Rac1) and p21 protein-activated kinase 1 (PAK1). The present study explores whether UA can modify actin cytoskeleton in cancer cells. METHODS The effect of UA on globular over filamentous actin ratio is determined utilizing Western blotting, immunofluorescence, and flow cytometry. Rac1 and PAK1 levels are measured by quantitative RT-PCR and immunoblotting. As a result, a 24 h treatment with UA (20 µm) significantly decreased Rac1 and PAK1 transcript levels and activity, depolymerized actin and wound healing. The effect of UA on actin polymerization is mimicked by pharmacological inhibition of Rac1 and PAK1. The effect is also mirrored by knock down using siRNA. CONCLUSION UA leads to disruption of Rac1 and Pak1 activity with subsequent actin depolymerization and migration. Thus, use of dietary UA in cancer prevention or as adjuvant therapy is promising.
Collapse
Affiliation(s)
- Md Alauddin
- Department of Women's Health, Eberhard Karls University of Tuebingen, Tübingen, 72076, Germany
| | - Toshiyuki Okumura
- Department of Women's Health, Eberhard Karls University of Tuebingen, Tübingen, 72076, Germany.,Department of Obstetrics and Gynecology, Juntendo University School of Medicine, Tokyo, 113-8421, Japan
| | - Janet Rajaxavier
- Department of Women's Health, Eberhard Karls University of Tuebingen, Tübingen, 72076, Germany
| | - Shayan Khozooei
- Department of Women's Health, Eberhard Karls University of Tuebingen, Tübingen, 72076, Germany
| | - Simone Pöschel
- Image Stream Core Facility, Eberhard Karls University of Tuebingen, Tübingen, 72076, Germany
| | - Satoru Takeda
- Department of Obstetrics and Gynecology, Juntendo University School of Medicine, Tokyo, 113-8421, Japan
| | - Yogesh Singh
- Institute of Medical Genetics and Applied Genomics, Eberhard Karls University of Tuebingen, Tübingen, 72076, Germany
| | - Sara Y Brucker
- Department of Women's Health, Eberhard Karls University of Tuebingen, Tübingen, 72076, Germany
| | - Diethelm Wallwiener
- Department of Women's Health, Eberhard Karls University of Tuebingen, Tübingen, 72076, Germany
| | - André Koch
- Department of Women's Health, Eberhard Karls University of Tuebingen, Tübingen, 72076, Germany
| | - Madhuri S Salker
- Department of Women's Health, Eberhard Karls University of Tuebingen, Tübingen, 72076, Germany
| |
Collapse
|
|
37
|
Norden E, Heiss EH. Urolithin A gains in antiproliferative capacity by reducing the glycolytic potential via the p53/TIGAR axis in colon cancer cells. Carcinogenesis 2019; 40:93-101. [PMID: 30418550 PMCID: PMC6412115 DOI: 10.1093/carcin/bgy158] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2018] [Revised: 10/16/2018] [Accepted: 11/07/2018] [Indexed: 12/12/2022] Open
Abstract
Polyphenols have shown promising bioactivity in experimental in vitro and in vivo models for cancer chemoprevention. However, consumed orally, they are often transformed by gut microbes into new active principles with so far incompletely deciphered molecular mechanisms. Here, enterolacton, S-equol and urolithin A as representatives of metabolites of lignans, isoflavones and ellagitannins, respectively, were examined for their impact on HCT116 colon cancer cell growth, cooperativity with oxaliplatin and p53 dependency in vitro. Whereas enterolacton and S-equol (≤60 µM) did not elicit growth inhibition or positive cooperativity with oxaliplatin, urolithin A showed an IC50 value of 19 µM (72 h) and synergism with oxaliplatin. Urolithin A induced p53 stabilization and p53 target gene expression, and absence of p53 significantly dampened the antiproliferative effect of urolithin A (IC50(p53-/-) = 38 µM). P53 was dispensable for the G2/M arrest in HCT116 cells but required for induction of a senescence-like phenotype upon long-term exposure and for the observed synergism with oxaliplatin. Moreover, extracellular flux analyses and knockdown approaches uncovered a reduced glycolytic potential via the p53/TIGAR axis which was linked to the higher susceptibility of wildtype cells to urolithin A. Overall, the p53 status turned out to be an important determinant for the potential benefit of dietary ellagitannins in cancer chemoprevention or use in adjuvant therapy.
Collapse
Affiliation(s)
- Elisabeth Norden
- Department of Pharmacognosy, University of Vienna, Vienna, Austria
| | - Elke H Heiss
- Department of Pharmacognosy, University of Vienna, Vienna, Austria
| |
Collapse
|
|
38
|
Shahraki A, Ebrahimi A. Ellagitannin derivatives and some conjugated metabolites: aqueous-DMSO proton affinities and acidity constants. Struct Chem 2019. [DOI: 10.1007/s11224-019-1284-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
|
|
39
|
Lv MY, Shi CJ, Pan FF, Shao J, Feng L, Chen G, Ou C, Zhang JF, Fu WM. Urolithin B suppresses tumor growth in hepatocellular carcinoma through inducing the inactivation of Wnt/β-catenin signaling. J Cell Biochem 2019; 120:17273-17282. [PMID: 31218741 DOI: 10.1002/jcb.28989] [Citation(s) in RCA: 50] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2019] [Revised: 04/08/2019] [Accepted: 04/11/2019] [Indexed: 12/16/2022]
Abstract
Consumption of dietary ellagitannins (ETs) has been proven to benefit multiple chronic health disorders including cancers and cardiovascular diseases. Urolithins, gut microbiota metabolites derived from ETs, are considered as the molecules responsible for these health effects. Previous studies have demonstrated that urolithins exhibit antiproliferative effects on prostate, breast, and colon cancers. However, as for hepatocellular carcinoma (HCC), it remains elusive. Herein, we aim to investigate the function of urolithin B (UB), a member of urolithins family, in HCC. The effects of UB on cell viability, cell cycle and apoptosis were evaluated in HCC cells, and we found UB could inhibit the proliferation of HCC cells, which resulted from cell cycle arrest and apoptosis. Furthermore, UB could increase phosphorylated β-catenin expression and block its translocation from nuclear to cytoplasm, thus inducing the inactivation of Wnt/β-catenin signaling. Using a xenograft mice model, UB was found to suppress tumor growth in vivo. In conclusion, our data demonstrated that UB could inhibit the proliferation of HCC cells in vitro and in vivo via inactivating Wnt/β-catenin signaling, suggesting UB could be a promising candidate in the development of anticancer drugs targeting HCC.
Collapse
Affiliation(s)
- Min-Yi Lv
- Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, People's Republic of China.,School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, People's Republic of China
| | - Chuan-Jian Shi
- Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, People's Republic of China.,School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, People's Republic of China
| | - Fei-Fei Pan
- Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, People's Republic of China.,School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, People's Republic of China
| | - Jiang Shao
- Key Laboratory of Orthopaedics and Traumatology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China.,Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China
| | - Lu Feng
- Department of Orthopaedics and Traumatology, Faculty of Medicine, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, People's Republic of China
| | - Guoqin Chen
- Department of Central Hospital of Panyu, Cardiovascular Medicine, Guangzhou, People's Republic of China
| | - Caiwen Ou
- Zhujiang Hospital, Southern Medical University, Key Laboratory of Construction and Detection of Guangdong Province, Guangdong Province Center of Biomedical Engineering for Cardiovascular Diseases, No. 1023, Shatai Nan Road, Guangzhou, People's Republic of China
| | - Jin-Fang Zhang
- Key Laboratory of Orthopaedics and Traumatology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China.,Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China
| | - Wei-Ming Fu
- Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, People's Republic of China.,School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, People's Republic of China
| |
Collapse
|
|
40
|
Gontijo DC, Gontijo PC, Brandão GC, Diaz MAN, de Oliveira AB, Fietto LG, Leite JPV. Antioxidant study indicative of antibacterial and antimutagenic activities of an ellagitannin-rich aqueous extract from the leaves of Miconia latecrenata. JOURNAL OF ETHNOPHARMACOLOGY 2019; 236:114-123. [PMID: 30853643 DOI: 10.1016/j.jep.2019.03.007] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/18/2018] [Revised: 03/04/2019] [Accepted: 03/04/2019] [Indexed: 06/09/2023]
Abstract
Ethnopharmacological relevance; Several plant species of Miconia genus are commonly used in Brazilian folk medicine as anti-inflammatory agents and for the treatment of infectious diseases. Infusions and extracts of Miconia species are also reported as analgesic, antimicrobial, antimalarial, antioxidant, anti-inflammatory, antinociceptive, antimutagenic, and antitumoral. Aim of the study; To determine the phytochemical composition of an aqueous extract of Miconia latecrenata leaves and to evaluate its antioxidant, antibacterial, antimutagenic and antigenotoxic activities. Materials and Methods; The following methods were used for the different effects: I) antioxidant - β-carotene/linoleic acid, lipid peroxidation, and DPPH• radical scavenging; II) antibacterial - agar well diffusion and MIC methods); III) antimutagenic assays - Ames Test; and IV) antigenotoxic - Plasmid cleavage test. The phytochemical analysis and phenolic quantification were carried out by UPLC-DAD-ESI-MS/MS and colorimetry, respectively. In addition, statistical correlation analysis was performed aiming to evaluate the Pearson correlation between phenolic compounds and biological assays. Results; A high content of tannins was observed and the ellagitannin isomers of 1,2,3,5-tris-galloyl-4,6-HHDP-glucose were identified as the main constituents of the leaves aqueous extract. High antioxidant effect, in different tests, high antibacterial activity to gram-positive and negative strains, as well as high antimutagenic activity were observed. Statistical analysis showed a high Pearson correlation for the tannin content in relation to the results of the antioxidant and antibacterial tests. In general, the antioxidant action of the aqueous extract showed low correlation with the antimutagenic activity. Conclusions; The present results confirmed the expectations regarding the pharmacological profile of M. latecrenata supporting its therapeutic potential in relation to ROS/RNS related disorders. Furthermore, the phenolic compounds of M. latecrenata can act, in turn, minimizing or inhibiting the biological macromolecules damage, especially DNA.
Collapse
Affiliation(s)
- Douglas Costa Gontijo
- Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Pampulha, CEP, 31270-901, Belo Horizonte, MG, Brazil; Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Viçosa, Av. P.H. Rolfs, s/n - Campus Universitário, CEP, 36570-000, Viçosa, MG, Brazil
| | - Pablo Costa Gontijo
- Setor de Agronomia, Instituto Federal Goiano, Rodovia Sul Goiana, Km 01, CEP, 75901-970, Rio Verde, GO, Brazil
| | - Geraldo Célio Brandão
- Escola de Farmácia, Universidade Federal de Ouro Preto, Morro do Cruzeiro, s/n, CEP, 35400-000, Ouro Preto, MG, Brazil
| | - Marisa Alves Nogueira Diaz
- Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Viçosa, Av. P.H. Rolfs, s/n - Campus Universitário, CEP, 36570-000, Viçosa, MG, Brazil
| | - Alaíde Braga de Oliveira
- Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Pampulha, CEP, 31270-901, Belo Horizonte, MG, Brazil
| | - Luciano Gomes Fietto
- Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Viçosa, Av. P.H. Rolfs, s/n - Campus Universitário, CEP, 36570-000, Viçosa, MG, Brazil
| | - João Paulo Viana Leite
- Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Viçosa, Av. P.H. Rolfs, s/n - Campus Universitário, CEP, 36570-000, Viçosa, MG, Brazil.
| |
Collapse
|
|
41
|
Gurdon C, Poulev A, Armas I, Satorov S, Tsai M, Raskin I. Genetic and Phytochemical Characterization of Lettuce Flavonoid Biosynthesis Mutants. Sci Rep 2019; 9:3305. [PMID: 30824720 PMCID: PMC6397293 DOI: 10.1038/s41598-019-39287-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2018] [Accepted: 01/22/2019] [Indexed: 12/24/2022] Open
Abstract
We previously developed red lettuce (Lactuca sativa L.) cultivars with high flavonoid and phenolic acid content and demonstrated their anti-diabetic effect. Here we report on developing three fertile and true-breeding lettuce lines enriched with flavonoids with reported beneficial health effects. These lines were identified in a segregating population of EMS-mutagenized red lettuce and characterized biochemically and genetically. Change in red coloration was used as a visual indicator of a mutation in a flavonoid pathway gene, leading to accumulation of flavonoid precursors of red anthocyanins. Pink-green kaempferol overproducing kfoA and kfoB mutants accumulated kaempferol to 0.6-1% of their dry weight, higher than in any vegetable reported. The yellow-green naringenin chalcone overproducing mutant (nco) accumulated naringenin chalcone, not previously reported in lettuce, to 1% dry weight, a level only observed in tomato peel. Kfo plants carried a mutation in the FLAVONOID-3' HYDROXYLASE (F3'H) gene, nco in CHALCONE ISOMERASE (CHI). This work demonstrates how non-GMO approaches can transform a common crop plant into a functional food with possible health benefits.
Collapse
Affiliation(s)
- Csanad Gurdon
- Department of Plant Biology, Rutgers University, 59 Dudley Road, New Brunswick, NJ, 08901-8520, USA.
| | - Alexander Poulev
- Department of Plant Biology, Rutgers University, 59 Dudley Road, New Brunswick, NJ, 08901-8520, USA
| | - Isabel Armas
- Department of Plant Biology, Rutgers University, 59 Dudley Road, New Brunswick, NJ, 08901-8520, USA
| | - Shukhratdzhon Satorov
- Department of Plant Biology, Rutgers University, 59 Dudley Road, New Brunswick, NJ, 08901-8520, USA
| | - Meg Tsai
- Department of Plant Biology, Rutgers University, 59 Dudley Road, New Brunswick, NJ, 08901-8520, USA
| | - Ilya Raskin
- Department of Plant Biology, Rutgers University, 59 Dudley Road, New Brunswick, NJ, 08901-8520, USA
| |
Collapse
|
|
42
|
Microbial Metabolites in Cancer Promotion or Prevention. MICROBIOME AND CANCER 2019. [DOI: 10.1007/978-3-030-04155-7_15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
|
|
43
|
Urolithin A Is a Dietary Microbiota-Derived Human Aryl Hydrocarbon Receptor Antagonist. Metabolites 2018; 8:metabo8040086. [PMID: 30501068 PMCID: PMC6315438 DOI: 10.3390/metabo8040086] [Citation(s) in RCA: 59] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2018] [Revised: 11/19/2018] [Accepted: 11/27/2018] [Indexed: 12/16/2022] Open
Abstract
Urolithins (e.g., UroA and B) are gut microbiota-derived metabolites of the natural polyphenol ellagic acid. Urolithins are associated with various health benefits, including attenuation of inflammatory signaling, anti-cancer effects and repression of lipid accumulation. The molecular mechanisms underlying the beneficial effects of urolithins remain unclear. We hypothesize that some of the human health benefits of urolithins are mediated through the aryl hydrocarbon receptor (AHR). Utilizing a cell-based reporter system, we tested urolithins for the capacity to modulate AHR activity. Cytochrome P450 1A1 (CYP1A1) mRNA levels were assessed by real-time quantitative polymerase chain reaction. Competitive ligand binding assays were performed to determine whether UroA is a direct ligand for the AHR. Subcellular AHR protein levels were examined utilizing immunoblotting analysis. AHR expression was repressed in Caco-2 cells by siRNA transfection to investigate AHR-dependency. UroA and B were able to antagonize 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced AHR-mediated transcriptional activity. Furthermore, UroA and B attenuated TCDD-mediated stimulation of CYP1A1 mRNA levels. In addition, competitive ligand binding assays characterized UroA as a direct AHR ligand. Consistent with other AHR antagonists, UroA failed to induce AHR retention in the nucleus. AHR is necessary for UroA-mediated attenuation of cytokine-induced interleukin 6 (IL6) and prostaglandin-endoperoxide synthase 2 (PTGS2) expression in Caco-2 cells. Here we identified UroA as the first dietary-derived human selective AHR antagonist produced by the gut microbiota through multi-step metabolism. Furthermore, previously reported anti-inflammatory activity of UroA may at least in part be mediated through AHR.
Collapse
|
|
44
|
Totiger TM, Srinivasan S, Jala VR, Lamichhane P, Dosch AR, Gaidarski AA, Joshi C, Rangappa S, Castellanos J, Vemula PK, Chen X, Kwon D, Kashikar N, VanSaun M, Merchant NB, Nagathihalli NS. Urolithin A, a Novel Natural Compound to Target PI3K/AKT/mTOR Pathway in Pancreatic Cancer. Mol Cancer Ther 2018; 18:301-311. [PMID: 30404927 DOI: 10.1158/1535-7163.mct-18-0464] [Citation(s) in RCA: 82] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2018] [Revised: 09/06/2018] [Accepted: 10/29/2018] [Indexed: 12/29/2022]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy and is highly resistant to standard treatment regimens. Targeted therapies against KRAS, a mutation present in an overwhelming majority of PDAC cases, have been largely ineffective. However, inhibition of downstream components in the KRAS signaling cascade provides promising therapeutic targets in the management of PDAC and warrants further exploration. Here, we investigated Urolithin A (Uro A), a novel natural compound derived from pomegranates, which targets numerous kinases downstream of KRAS, in particular the PI3K/AKT/mTOR signaling pathways. We showed that treatment of PDAC cells with Uro A blocked the phosphorylation of AKT and p70S6K in vitro, successfully inhibited the growth of tumor xenografts, and increased overall survival of Ptf1aCre/+;LSL-KrasG12D/+;Tgfbr2flox/flox (PKT) mice compared with vehicle or gemcitabine therapy alone. Histologic evaluation of these Uro A-treated tumor samples confirmed mechanistic actions of Uro A via decreased phosphorylation of AKT and p70S6K, reduced proliferation, and increased cellular apoptosis in both xenograft and PKT mouse models. In addition, Uro A treatment reprogrammed the tumor microenvironment, as evidenced by reduced levels of infiltrating immunosuppressive cell populations such as myeloid-derived suppressor cells, tumor-associated macrophages, and regulatory T cells. Overall, this work provides convincing preclinical evidence for the utility of Uro A as a therapeutic agent in PDAC through suppression of the PI3K/AKT/mTOR pathway.
Collapse
Affiliation(s)
- Tulasigeri M Totiger
- Department of Surgery, University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, Miami, Florida
| | - Supriya Srinivasan
- Department of Surgery, University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, Miami, Florida
| | - Venkatakrishna R Jala
- Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky
| | - Purushottam Lamichhane
- Department of Surgery, University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, Miami, Florida
| | - Austin R Dosch
- Department of Surgery, University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, Miami, Florida
| | - Alexander A Gaidarski
- Department of Surgery, University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, Miami, Florida
| | - Chandrashekhar Joshi
- Department of Surgery, University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, Miami, Florida
| | - Shobith Rangappa
- Adichunchanagiri Institute for Molecular Medicine, AIMS, Karnataka, India
| | - Jason Castellanos
- Department of Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee
| | - Praveen Kumar Vemula
- Institute for Stem Cell Biology and Regenerative Medicine (inStem), Bangalore, Karnataka, India
| | - Xi Chen
- Department of Public Health, University of Miami Miller School of Medicine, Miami, Florida
| | - Deukwoo Kwon
- Department of Public Health, University of Miami Miller School of Medicine, Miami, Florida
| | - Nilesh Kashikar
- Department of Pathology, University of Colorado, Denver, Colorado
| | - Michael VanSaun
- Department of Surgery, University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, Miami, Florida
| | - Nipun B Merchant
- Department of Surgery, University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, Miami, Florida
| | - Nagaraj S Nagathihalli
- Department of Surgery, University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, Miami, Florida.
| |
Collapse
|
|
45
|
Koval A, Pieme CA, Queiroz EF, Ragusa S, Ahmed K, Blagodatski A, Wolfender JL, Petrova TV, Katanaev VL. Tannins from Syzygium guineense suppress Wnt signaling and proliferation of Wnt-dependent tumors through a direct effect on secreted Wnts. Cancer Lett 2018; 435:110-120. [PMID: 30098400 DOI: 10.1016/j.canlet.2018.08.003] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2017] [Revised: 06/12/2018] [Accepted: 07/31/2018] [Indexed: 02/07/2023]
Abstract
Triple-negative breast cancer (TNBC) and colon cancer (CC) are two stigmatic examples of poorly treatable tumors, whose progression critically depends upon hyperactivation of the Wnt signaling. Development of specific anti-Wnt inhibitors is required to develop drugs against these and other Wnt-dependent cancers. Natural products, especially plants, have been used for the treatment of various diseases from ancient times. We examined extracts from several indigenous Cameroonian herbs and tested their effects on proliferation and Wnt signaling in TNBC and CC cells. Extracts from "fruit rouge", Syzygium guineense Wall. (Myrtaceae), demonstrated a strong activity against these cancer cells, as well as CC organoids. We found TNBC cells to significantly upregulate expression of Wnt3a, and the effects of S. guineense extracts on TNBC cell proliferation correlated with inhibition of the Wnt3a-induced β-catenin stabilization and transcriptional response. HPLC analysis revealed that the active components belong to tannins. We found a direct destabilizing effect of S. guineense extract on Wnt3a and other Wnt proteins, identifying a novel mechanism of action of tannins on the Wnt signaling pathway and cancer cell proliferation. Being edible, this African plant may have an important cancer-preventive nutritional value.
Collapse
Affiliation(s)
- Alexey Koval
- Department of Pharmacology and Toxicology, University of Lausanne, Switzerland
| | - Constant A Pieme
- Department of Pharmacology and Toxicology, University of Lausanne, Switzerland; Department of Biochemistry and Physiological Sciences, University of Yaounde I, Cameroon
| | | | - Simone Ragusa
- (d)Department of Oncology, Ludwig Cancer Research, Lausanne Branch, and Institute of Pathology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Epalinges, Switzerland
| | - Kamal Ahmed
- Department of Pharmacology and Toxicology, University of Lausanne, Switzerland
| | - Artem Blagodatski
- Department of Pharmacology and Toxicology, University of Lausanne, Switzerland; School of Biomedicine, Far Eastern Federal University, Vladivostok, Russia
| | | | - Tatiana V Petrova
- (d)Department of Oncology, Ludwig Cancer Research, Lausanne Branch, and Institute of Pathology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Epalinges, Switzerland
| | - Vladimir L Katanaev
- Department of Pharmacology and Toxicology, University of Lausanne, Switzerland; School of Biomedicine, Far Eastern Federal University, Vladivostok, Russia.
| |
Collapse
|
|
46
|
Singh B, Singh JP, Kaur A, Singh N. Insights into the phenolic compounds present in jambolan (Syzygium cumini) along with their health-promoting effects. Int J Food Sci Technol 2018. [DOI: 10.1111/ijfs.13841] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Affiliation(s)
- Balwinder Singh
- P.G. Department of Biotechnology; Khalsa College; Amritsar 143002 Punjab India
| | - Jatinder Pal Singh
- Department of Food Science and Technology; Guru Nanak Dev University; Amritsar 143005 Punjab India
| | - Amritpal Kaur
- Department of Food Science and Technology; Guru Nanak Dev University; Amritsar 143005 Punjab India
| | - Narpinder Singh
- Department of Food Science and Technology; Guru Nanak Dev University; Amritsar 143005 Punjab India
| |
Collapse
|
|
47
|
Qiu Z, Zhou J, Zhang C, Cheng Y, Hu J, Zheng G. Antiproliferative effect of urolithin A, the ellagic acid-derived colonic metabolite, on hepatocellular carcinoma HepG2.2.15 cells by targeting Lin28a/let-7a axis. ACTA ACUST UNITED AC 2018; 51:e7220. [PMID: 29742265 PMCID: PMC5972012 DOI: 10.1590/1414-431x20187220] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2017] [Accepted: 02/02/2018] [Indexed: 02/07/2023]
Abstract
An abnormality in the Lin28/let-7a axis is relevant to the progression of
hepatitis B virus (HBV)-positive hepatocellular carcinoma (HCC), which could be
a novel therapeutic target for this malignant tumor. The present study aimed to
investigate the antiproliferative and anti-invasive effects of urolithin A in a
stable full-length HBV gene integrated cell line HepG2.2.15 using CCK-8 and
transwell assays. The RNA and protein expressions of targets were assessed by
quantitative PCR and western blot, respectively. Results revealed that urolithin
A induced cytotoxicity in HepG2.2.15 cells, which was accompanied by the
cleavage of caspase-3 protein and down-regulation of Bcl-2/Bax ratio. Moreover,
urolithin A suppressed the protein expressions of Sp-1, Lin28a, and Zcchc11, and
elevated the expression of microRNA let-7a. Importantly, urolithin A also
regulated the Lin28a/let-7a axis in transient HBx-transfected HCC HepG2 cells.
Furthermore, urolithin A decelerated the HepG2.2.15 cell invasion, which was
involved in suppressing the let-7a downstream factors HMGA2 and K-ras. These
findings indicated that urolithin A exerted the antiproliferative effect by
regulating the Lin28a/let-7a axis and may be a potential supplement for
HBV-infected HCC therapy.
Collapse
Affiliation(s)
- Zhenpeng Qiu
- College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China
| | - Junxuan Zhou
- College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China
| | - Cong Zhang
- College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China
| | - Ye Cheng
- Hubei Engineering Research Center of Viral Vector, Wuhan Institute of Bioengineering, Wuhan, China
| | - Junjie Hu
- College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China
| | - Guohua Zheng
- Key Laboratory of Chinese Medicine Resource and Compound Prescription, Ministry of Education, Hubei University of Chinese Medicine, Wuhan, China
| |
Collapse
|
|
48
|
Israel BB, Tilghman SL, Parker-Lemieux K, Payton-Stewart F. Phytochemicals: Current strategies for treating breast cancer. Oncol Lett 2018; 15:7471-7478. [PMID: 29755596 DOI: 10.3892/ol.2018.8304] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2017] [Accepted: 11/20/2017] [Indexed: 12/11/2022] Open
Abstract
Females with early-stage metastatic, estrogen-dependent breast cancer are generally treated with surgery, radiation and chemotherapy, or with more targeted approaches such as aromatase inhibitors (anastrozole or letrozole) or anti-estrogens (tamoxifen). Despite widespread successful usage of these agents for the treatment of breast cancer, resistance, tumor relapse and metastasis remain the principal causes of mortality for patients with breast cancer. While numerous groups have made major contributions toward an improved understanding of resistance mechanisms, the currently insufficient grasp of the most critical pathways involved in resistance is evident in the inability to adequately treat and drastically improve patient outcomes in females with hormone-refractory breast cancer, including triple negative breast cancer. Therefore, further investigation of novel therapeutic approaches is paramount to reveal previously unconsidered agents that could be utilized to treat metastatic disease. Numerous naturally occurring phytochemicals have recently gained interest as potential therapeutic breast cancer agents appear to directly affect estrogen-dependent and estrogen-independent breast cancer cell proliferation, potentially via affecting breast cancer stem cell populations. While numerous natural compounds have exhibited promise, they are limited by their bioavailability. Therefore, to effectively treat future hormone-refractory breast tumors, it is critical to adequately refine and formulate these agents for effective therapeutic use and delivery. Herein, the literature on the current state of phytochemicals is reviewed, including their limitations and potential as targeted therapies for breast cancer.
Collapse
Affiliation(s)
- Bridg'ette B Israel
- Division of Basic Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA
| | - Syreeta L Tilghman
- Division of Basic Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA
| | - Kitani Parker-Lemieux
- Division of Basic Pharmaceutical Sciences, College of Pharmacy, Xavier University of Louisiana, New Orleans, LA 70125, USA
| | - Florastina Payton-Stewart
- Division of Mathematical and Physical Sciences, College of Arts and Sciences, Xavier University of Louisiana, New Orleans, LA 70125, USA
| |
Collapse
|
|
49
|
Meng C, Bai C, Brown TD, Hood LE, Tian Q. Human Gut Microbiota and Gastrointestinal Cancer. GENOMICS PROTEOMICS & BIOINFORMATICS 2018. [PMID: 29474889 DOI: 10.1016/j.gpb.2017.06.002.] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Abstract
Human gut microbiota play an essential role in both healthy and diseased states of humans. In the past decade, the interactions between microorganisms and tumors have attracted much attention in the efforts to understand various features of the complex microbial communities, as well as the possible mechanisms through which the microbiota are involved in cancer prevention, carcinogenesis, and anti-cancer therapy. A large number of studies have indicated that microbial dysbiosis contributes to cancer susceptibility via multiple pathways. Further studies have suggested that the microbiota and their associated metabolites are not only closely related to carcinogenesis by inducing inflammation and immune dysregulation, which lead to genetic instability, but also interfere with the pharmacodynamics of anticancer agents. In this article, we mainly reviewed the influence of gut microbiota on cancers in the gastrointestinal (GI) tract (including esophageal, gastric, colorectal, liver, and pancreatic cancers) and the regulation of microbiota by diet, prebiotics, probiotics, synbiotics, antibiotics, or the Traditional Chinese Medicine. We also proposed some new strategies in the prevention and treatment of GI cancers that could be explored in the future. We hope that this review could provide a comprehensive overview of the studies on the interactions between the gut microbiota and GI cancers, which are likely to yield translational opportunities to reduce cancer morbidity and mortality by improving prevention, diagnosis, and treatment.
Collapse
Affiliation(s)
- Changting Meng
- Institute for Systems Biology, Seattle, WA 98109, USA; Department of Oncology, Peking Union Medical College Hospital, Beijing 100730, China
| | - Chunmei Bai
- Department of Oncology, Peking Union Medical College Hospital, Beijing 100730, China
| | | | - Leroy E Hood
- Institute for Systems Biology, Seattle, WA 98109, USA; Swedish Cancer Institute, Seattle, WA 98104, USA
| | - Qiang Tian
- Institute for Systems Biology, Seattle, WA 98109, USA; P4 Medicine Institute, Seattle, WA 98109, USA.
| |
Collapse
|
|
50
|
Meng C, Bai C, Brown TD, Hood LE, Tian Q. Human Gut Microbiota and Gastrointestinal Cancer. GENOMICS, PROTEOMICS & BIOINFORMATICS 2018; 16:33-49. [PMID: 29474889 PMCID: PMC6000254 DOI: 10.1016/j.gpb.2017.06.002] [Citation(s) in RCA: 275] [Impact Index Per Article: 39.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/08/2017] [Revised: 06/08/2017] [Accepted: 07/04/2017] [Indexed: 02/06/2023]
Abstract
Human gut microbiota play an essential role in both healthy and diseased states of humans. In the past decade, the interactions between microorganisms and tumors have attracted much attention in the efforts to understand various features of the complex microbial communities, as well as the possible mechanisms through which the microbiota are involved in cancer prevention, carcinogenesis, and anti-cancer therapy. A large number of studies have indicated that microbial dysbiosis contributes to cancer susceptibility via multiple pathways. Further studies have suggested that the microbiota and their associated metabolites are not only closely related to carcinogenesis by inducing inflammation and immune dysregulation, which lead to genetic instability, but also interfere with the pharmacodynamics of anticancer agents. In this article, we mainly reviewed the influence of gut microbiota on cancers in the gastrointestinal (GI) tract (including esophageal, gastric, colorectal, liver, and pancreatic cancers) and the regulation of microbiota by diet, prebiotics, probiotics, synbiotics, antibiotics, or the Traditional Chinese Medicine. We also proposed some new strategies in the prevention and treatment of GI cancers that could be explored in the future. We hope that this review could provide a comprehensive overview of the studies on the interactions between the gut microbiota and GI cancers, which are likely to yield translational opportunities to reduce cancer morbidity and mortality by improving prevention, diagnosis, and treatment.
Collapse
Affiliation(s)
- Changting Meng
- Institute for Systems Biology, Seattle, WA 98109, USA; Department of Oncology, Peking Union Medical College Hospital, Beijing 100730, China
| | - Chunmei Bai
- Department of Oncology, Peking Union Medical College Hospital, Beijing 100730, China
| | | | - Leroy E Hood
- Institute for Systems Biology, Seattle, WA 98109, USA; Swedish Cancer Institute, Seattle, WA 98104, USA
| | - Qiang Tian
- Institute for Systems Biology, Seattle, WA 98109, USA; P4 Medicine Institute, Seattle, WA 98109, USA.
| |
Collapse
|