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Current Drug Targets


ISSN (Print): 1389-4501
ISSN (Online): 1873-5592

Review Article

The Epigenetic Modification of Epigallocatechin Gallate (EGCG) on Cancer

Author(s): Linqi Yang, Wenqi Zhang, Saiyam Chopra, Deeepjyot Kaur, Huibing Wang, Meng Li, Pingping Chen* and Wei Zhang*

Volume 21 , Issue 11 , 2020

Page: [1099 - 1104] Pages: 6

DOI: 10.2174/1389450121666200504080112

Price: $65


Among the major components of green tea, epigallocatechin-3-gallate (EGCG) is the most effective for its anti-cancer characteristics. The bulk of studies provide the mechanisms of suppressive function of EGCG are involved in alteration of cancer cell cycle, development, and apoptosis through activation/inhibition of several signal pathways.

Another mechanism that explains the multiple effects exerted by EGCG in cancer is the epigenetic change by DNA methylation or methyltransferases, histone acetylation or deacetylases, and no coding RNAs (micoRNAs). Furthermore, decontrolled expression of miRNA transcription has been tested to be directly regulated by oncogenic and tumor-suppressor transcription factors. Recently, several proteins have been identified as miRNA direct interactors by EGCG. However, the mechanisms explaining the action of miRNA being modulated by EGCG have not been completely understood yet. This review summarizes the state of epigenetic change being modulated by EGCG in a variety of cancers and oncogenic and tumor-suppressor transcription factors.

Keywords: Epigallocatechin-gallate (EGCG), micoRNA, cancer, epigenetic regulators, methyltransferases, miRNA.

Graphical Abstract
Negri A, Naponelli V, Rizzi F, Bettuzzi S. Molecular targets of epigallocatechin-gallate (egcg): a special focus on signal transduction and cancer. Nutrients 2018; 10(12): 1936.
[] [PMID: 30563268]
Sur S, Panda CK. Molecular aspects of cancer chemopreventive and therapeutic efficacies of tea and tea polyphenols. Nutrition 2017; 43-44: 8-15.
[] [PMID: 28935149]
Hu Qian, Xiang Chang Rong, Yan , et al. (-)-Epigallocatechin-3-gallate Induces Cancer Cell Apoptosis Via Acetylation of Amyloid Precursor Protein. Med Oncol 2015; 32(1): 390.
Michael Daniel1, Trygve O, Tollefsbol. Epigenetic Linkage of Aging, Cancer and Nutrition. Experimental Biology 2015; 218(Pt 1): 59-70.
[] [PMID: 25568452]
Singh V, Sharma P, Capalash N. DNA methyltransferase-1 inhibitors as epigenetic therapy for cancer. Curr Cancer Drug Targets 2013; 13(4): 379-99.
[] [PMID: 23517596]
Min NY, Kim J-H, Choi J-H, et al. Selective death of cancer cells by preferential induction of reactive oxygen species in response to (-)-epigallocatechin-3-gallate. Biochem Biophys Res Commun 2012; 421(1): 91-7.
[] [PMID: 22487794]
Li Y, Tollefsbol TO. Impact on DNA methylation in cancer prevention and therapy by bioactive dietary components. Curr Med Chem 2010; 17(20): 2141-51.
[] [PMID: 20423306]
Qian B-J, Tian C-C, Ling X-H, et al. miRNA-150-5p associate with antihypertensive effect of epigallocatechin-3-gallate revealed by aorta miRNome analysis of spontaneously hypertensive rat. Life Sci 2018; 203: 193-202.
[] [PMID: 29705350]
Chen Y, Huang L, Wang L, Chen L, Ren W, Zhou W. Differential expression of microRNAs contributed to the health efficacy of EGCG in in vitro subarachnoid hemorrhage model. Food Funct 2017; 8(12): 4675-83.
[] [PMID: 29160895]
Rashidi B, Malekzadeh M, Goodarzi M, Masoudifar A, Mirzaei H. Green tea and its anti-angiogenesis effects. Biomed Pharmacother 2017; 89: 949-56.
[] [PMID: 28292023]
Baselga-Escudero L, Blade C, Ribas-Latre A, et al. Resveratrol and EGCG bind directly and distinctively to miR-33a and miR-122 and modulate divergently their levels in hepatic cells. Nucleic Acids Res 2014; 42(2): 882-92.
[] [PMID: 24165878]
Zhoua Dong-Hu Wanga, Xuemin , Qing Fenga. EGCG Enhances the Efficacy of Cisplatin by Downregulating hsa-miR-98-5p in NSCLC A549 Cells nutrition andcancer 2014; 66(4): 636-44.
Sethi Sajiv , Li Yiwei, Sarkar FazlulH. Regulating miRNA by Natural Agents as a New Strategy for Cancer Treatment. [j] Curr Drug Targets 2013; 14(10): 1167-74.
Wang Y, Li Y, Liu X, Cho WCS. Genetic and epigenetic studies for determining molecular targets of natural product anticancer agents. Curr Cancer Drug Targets 2013; 13(5): 506-18.
[] [PMID: 23597195]
Arola-Arnal A, Bladé C. Proanthocyanidins modulate microRNA expression in human HepG2 cells. PLoS One 2011; 6(10)e25982
[] [PMID: 21998738]
Tsang WP, Kwok TT. Epigallocatechin gallate up-regulation of miR-16 and induction of apoptosis in human cancer cells. J Nutr Biochem 2010; 21(2): 140-6.
[] [PMID: 19269153]
Shilpi A, Parbin S, Sengupta D, et al. Mechanisms of DNA methyltransferase-inhibitor interactions: Procyanidin B2 shows new promise for therapeutic intervention of cancer. Chem Biol Interact 2015; 233: 122-38.
[] [PMID: 25839702]
Sheng J, Shi W, Guo H, et al. The Inhibitory Effect of (-)-Epigallocatechin-3-Gallate on Breast Cancer Progression via Reducing SCUBE2 Methylation and DNMT Activity. Molecules 2019; 24(16)E2899
[] [PMID: 31404982]
Lewis KA, Jordan HR, Tollefsbol TO. Effects of SAHA and EGCG on Growth Potentiation of Triple-Negative Breast Cancer Cells. Cancers (Basel) 2018; 11(1)E23.
[] [PMID: 30591655]
Lubecka K, Kaufman-Szymczyk A, Cebula-Obrzut B, Smolewski P, Szemraj J, Fabianowska-Majewska K. Novel Clofarabine-Based Combinations with Polyphenols Epigenetically Reactivate Retinoic Acid Receptor Beta, Inhibit Cell Growth, and Induce Apoptosis of Breast Cancer Cells. Int J Mol Sci 2018; 19(12)E3970
[] [PMID: 30544666]
Gianfredi V, Vannini S, Moretti M, et al. Sulforaphane and Epigallocatechin Gallate Restore Estrogen Receptor Expression by Modulating Epigenetic Events in the Breast Cancer Cell Line MDA-MB-231: A Systematic Review and Meta-Analysis. J Nutrigenet Nutrigenomics 2017; 10(3-4): 126-35.
[] [PMID: 29040973]
Gianfredi V, Nucci D, Vannini S, Villarini M, Moretti M. In vitro Biological Effects of Sulforaphane (SFN), Epigallocatechin-3-gallate (EGCG), and Curcumin on Breast Cancer Cells: A Systematic Review of the Literature. Nutr Cancer 2017; 69(7): 969-78.
[] [PMID: 28872903]
Li Y, Meeran SM, Tollefsbol TO. Combinatorial bioactive botanicals re-sensitize tamoxifen treatment in ER-negative breast cancer via epigenetic reactivation of ERα expression. Sci Rep 2017; 7(1): 9345.
[] [PMID: 28839265]
Deb G, Thakur VS, Limaye AM, Gupta S. Epigenetic induction of tissue inhibitor of matrix metalloproteinase-3 by green tea polyphenols in breast cancer cells. Mol Carcinog 2015; 54(6): 485-99.
[] [PMID: 24481780]
Tulika Tyagi Justin N. Treas, Prathap Kumar S. Mahalingaiah, Kamaleshwar P. Singh Potentiation of Growth Inhibition and Epigenetic Modulation by Combinationof Green Tea Polyphenol and 5-aza-20- deoxycytidine in Human Breast Cancer Cells. Breast Cancer Res Treat 2015; 149(3): 655-68.
[] [PMID: 25663548]
Khan SI, Aumsuwan P, Khan IA, Walker LA, Dasmahapatra AK. Epigenetic events associated with breast cancer and their prevention by dietary components targeting the epigenome. Chem Res Toxicol 2012; 25(1): 61-73.
[] [PMID: 21992498]
Meeran SM, Patel SN, Chan T-H, Tollefsbol TO. A novel prodrug of epigallocatechin-3-gallate: differential epigenetic hTERT repression in human breast cancer cells. Cancer Prev Res (Phila) 2011; 4(8): 1243-54.
[] [PMID: 21411498]
Li Y, Yuan Y-Y, Syed M. Meeran, Trygve O Tollefsbol. synergistic epigenetic reactivation of estrogen receptor-a (era) by combined green tea polyphenol and histone deacetylase inhibitor in era-negative breast cancer cells. Mol Cancer 2010; 9: 274.
[] [PMID: 20946668]
Pal D, Sur S, Roy R, Mandal S, Kumar Panda C. Epigallocatechin gallate in combination with eugenol or amarogentin shows synergistic chemotherapeutic potential in cervical cancer cell line. J Cell Physiol 2018; 234(1): 825-36.
[] [PMID: 30078217]
Munawwar AliKhan, Arif Hussain, Madhumitha Kedhari Sundaram, Usama Al Alami, Dian Gunasekera, Laveena Ramesh, Amina Hamza, Uzma Quraishi. (-)-E pigallocatechin-3-gallate Reverses the Expression of Various Tumor-suppressor Genes by Inhibiting DNA Methyltransferases and Histone Deacetylases in Human Cervical Cancer Cells. Oncol Rep 2015; 33(4): 1976-84.
[PMID: 25682960]
Zhu Y, Huang Y, Liu M, et al. Epigallocatechin gallate inhibits cell growth and regulates miRNA expression in cervical carcinoma cell lines infected with different high-risk human papillomavirus subtypes. Exp Ther Med 2019; 17(3): 1742-8.
[PMID: 30783443]
Gao Z, Xu Z, Hung MS, et al. Promoter demethylation of WIF-1 by epigallocatechin-3-gallate in lung cancer cells. Anticancer Res 2009; 29(6): 2025-30.
[PMID: 19528461]
Wang Hong, Bian Shengjie, Chung S. Green Tea Polyphenol EGCG Suppresses Lung Cancer Cell Growth through Upregulating miR-210 Expression caused by Stabilizing HIF-1a. Carcinogenesis 201 32(12): 1881-9.
[] [PMID: 21965273]
Giudice A, Montella M, Boccellino M, et al. Epigen etic Changes Induced by Green Tea Catechins are Associated with Prostate Cancer Current Molecular Medicine 2017; 17(6): 405-20.
[] [PMID: 29256350]
Deb G, Shankar E, Thakur VS, Lee E. Ponsky, Donald R.Bodne, Pingfu Fu, Sanjay Gupta. Green Tea-induced Epigenetic Reactivation of Tissue Inhibitor of Matrix Metalloproteinase-3 Suppresses Prostate Cancer Progression through Histon-modifying Enzymes. Mol Carcinog 2019; 58(7): 1194-207.
[] [PMID: 30854739]
Jiang P, Xu C, Chen L, et al. EGCG inhibits CSC-like properties through targeting miR-485/CD44 axis in A549-cisplatin resistant cells. Mol Carcinog 2018; 57(12): 1835-44.
[] [PMID: 30182373]
Pan Jiang, Chuyue XU, Lijun Chen , et al. Epigallocatechin-3-gallate inhibited cancer stem cell-like properties by targeting hsa-mir-485-5p/RXRα in lung cancer. Cell Biochem 2018; 119(10): 8623-35.
[] [PMID: 30058740]
Giudice A, Montella M, Boccellino M, et al. Epigenetic changes induced by green tea catechins a re associated with prostate cancer. Curr Mol Med 2017; 17(6): 405-20.
[PMID: 29256350]
Siddiqui IA, Asim M, Hafeez BB, Adhami VM, Tarapore RS, Mukhtar H. Green tea polyphenol EGCG blunts androgen receptor function in prostate cancer. FASEB J 2011; 25(4): 1198-207.
[] [PMID: 21177307]
Balasubramanian S, Scharadin TM, Han B, Xu W, Eckert RL. The Bmi-1 helix-turn and ring finger domains are required for Bmi-1 antagonism of (-) epigallocatechin-3-gallate suppression of skin cancer cell survival. Cell Signal 2015; 27(7): 1336-44.
[] [PMID: 25843776]
Nandakumar V, Vaid M, Katiyar SK. (-)-Epigallocatechin-3-gallate reactivates silenced tumor suppressor genes, Cip1/p21 and p16INK4a, by reducing DNA methylation and increasing histones acetylation in human skin cancer cells. Carcinogenesis 2011; 32(4): 537-44.
[] [PMID: 21209038]
Balasubramanian S, Adhikary G, Eckert RL. The Bmi-1 polycomb protein antagonizes the (-)-epigallocatechin-3-gallate-dependent suppression of skin cancer cell survival. Carcinogenesis 2010; 31(3): 496-503.
[] [PMID: 20015867]
IN-SOOK AN SUNGKWAN AN, SEYEON PARK , SUNG NAE. LEE4, SEUNGHEE BAE2. Involvement of microRNAs In epigallocatechin Gallate-mediated UVB Protection in Human Dermal Fibroblasts 2013; 29(1): 253-9.
Zhu K, Wang W. Green tea polyphenol EGCG suppresses osteosarcoma cell growth through upregulating miR-1. Tumour Biol 2016; 37(4): 4373-82.
[] [PMID: 26499783]
Huang D, Cui L, Ahmed S, et al. An overview of epigenetic agents and natural nutrition products targeting DNA methyltransferase, histone deacetylases and microRNAs. Food Chem Toxicol 2019; 123: 574-94.
[] [PMID: 30408543]
Yamada S, Tsukamoto S, Huang Y, et al. Epigallocatechin-3-O-gallate up-regulates microRNA-let-7b expression by activating 67-kDa laminin receptor signaling in melanoma cells. Sci Rep 2016; 6: 19225.
[] [PMID: 26754091]
Lelli D, Pedone C, Sahebkar A. Curcumin and treatment of melanoma: The potential role of microRNAs. Biomed Pharmacother 2017; 88: 832-4.
[] [PMID: 28167449]
Morris J, Moseley VR, Cabang AB, et al. Reduction in promotor methylation utilizing EGCG (epigallocatechin-3-gallate) restores RXRα expression in human colon cancer cells. Oncotarget 2016; 7(23): 35313-26.
[] [PMID: 27167203]
Saldanha SN, Kala R, Tollefsbol TO. Molecular mechanisms for inhibition of colon cancer cells by combined epigenetic-modulating epigallocatechin gallate and sodium butyrate. Exp Cell Res 2014; 324(1): 40-53.
[] [PMID: 24518414]
Sokolosky ML, Wargovich MJ. Homeostatic imbalance and colon cancer: the dynamic epigenetic interplay of inflammation, environmental toxins, and chemopreventive plant compounds. Front Oncol 2012; 2: 57.
[] [PMID: 22675672]
Kumazaki M, Noguchi S, Yasui Y, et al. Anti-cancer effects of naturally occurring compounds through modulation of signal transduction and miRNA expression in human colon cancer cells. J Nutr Biochem 2013; 24(11): 1849-58.
[] [PMID: 23954321]
Ying L, Yan F, Williams BR, et al. (-)-Epigallocatechin-3-gallate and EZH2 inhibitor GSK343 have similar inhibitory effects and mechanisms of action on colorectal cancer cells. Clin Exp Pharmacol Physiol 2018; 45(1): 58-67.
[] [PMID: 28925507]
Lee WJ, Shim JY, Zhu BT. Mechanisms for the inhibition of DNA methyltransferases by tea catechins and bioflavonoids. Mol Pharmacol 2005; 68(4): 1018-30.
[] [PMID: 16037419]
Landis-Piwowar K, Chen D, Chan TH, Dou QP. Inhibition of catechol-Omicron-methyltransferase activity in human breast cancer cells enhances the biological effect of the green tea polyphenol (-)-EGCG. Oncol Rep 2010; 24(2): 563-9.
[PMID: 20596647]
Mittal A, Pate MS, Wylie RC, Tollefsbol TO, Katiyar SK. EGCG down-regulates telomerase in human breast carcinoma MCF-7 cells, leading to suppression of cell viability and induction of apoptosis. Int J Oncol 2004; 24(3): 703-10.
[] [PMID: 14767556]
Smith LL, Coller HA, Roberts JM. Telomerase modulates expression of growth-controlling genes and enhances cell proliferation. Nat Cell Biol 2003; 5(5): 474-9.
[] [PMID: 12717449]
Liu Y, Ao X, Ding W, et al. Critical role of FOXO3a in carcinogenesis. Mol Cancer 2018; 17(1): 104.
[] [PMID: 30045773]
Belguise K, Guo S, Sonenshein GE. Activation of FOXO3a by the green tea polyphenol epigallocatechin-3-gallate induces estrogen receptor alpha expression reversing invasive phenotype of breast cancer cells. Cancer Res 2007; 67(12): 5763-70.
[] [PMID: 17575143]
Chung SS, Vadgama JV. Curcumin and epigallocatechin gallate inhibit the cancer stem cell phenotype via down-regulation of STAT3-NFκB signaling. Anticancer Res 2015; 35(1): 39-46.
[PMID: 25550533]
Groh IA, Chen C, Lüske C, Cartus AT, Esselen M. Plant polyphenols and oxidative metabolites of the herbal alkenylbenzene methyleugenol suppress histone deacetylase activity in human colon carcinoma cells. J Nutr Metab 2013; 2013: 821082-92.
[] [PMID: 23476753]

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