Abstract
EGCG, the most abundant catechins of green tea exhibits several beneficial impacts on human health and helps in the amelioration of various pathological conditions including cardiovascular diseases, obesity, and cancer. The anti-obesity potential of EGCG depends on its potent antioxidant property, lipid metabolism modulatory action, and adipogenesis inhibitory ability. Moreover, EGCG also exhibits promising anticancer activity against cancer of different origins by inhibiting various features of tumorigenesis such as proliferation, evasion of apoptosis, angiogenesis, invasion and migration, and multidrug resistance through altering various signaling pathways. Taken as a whole, in this book chapter, we have discussed the detailed known mechanisms of anti-obesity and anticancer activities of EGCG and have also provided information about several novel targets of EGCG.
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References
Aarsland A, Chinkes D, Wolfe RR (1996) Contributions of de novo synthesis of fatty acids to total VLDL-triglyceride secretion during prolonged hyperglycemia/hyperinsulinemia in normal man. J Clin Invest 98(9):2008–2017. https://doi.org/10.1172/JCI119005
Aboulwafa MM, Youssef FS, Gad HA, Altyar AE, Al-Azizi MM, Ashour ML (2019) A comprehensive insight on the health benefits and Phytoconstituents of Camellia sinensis and recent approaches for its quality control. Antioxidants (Basel) 8:10. https://doi.org/10.3390/antiox8100455
Aggarwal V, Tuli HS, Tania M, Srivastava S, Ritzer EE, Pandey A, Aggarwal D, Barwal TS, Jain A, Kaur G, Sak K, Varol M, Bishayee A (2020) Molecular mechanisms of action of epigallocatechin gallate in cancer: recent trends and advancement. Semin Cancer Biol. https://doi.org/10.1016/j.semcancer.2020.05.011
Ahmad B, Serpell CJ, Fong IL, Wong EH (2020) Molecular mechanisms of Adipogenesis: the anti-adipogenic role of AMP-activated protein kinase. Front Mol Biosci 7:76. https://doi.org/10.3389/fmolb.2020.00076
Ahmad N, Cheng P, Mukhtar H (2000a) Cell cycle dysregulation by green tea polyphenol epigallocatechin-3-gallate. Biochem Biophys Res Commun 275(2):328–334. https://doi.org/10.1006/bbrc.2000.3297
Ahmad N, Gupta S, Mukhtar H (2000b) Green tea polyphenol epigallocatechin-3-gallate differentially modulates nuclear factor kappaB in cancer cells versus normal cells. Arch Biochem Biophys 376(2):338–346. https://doi.org/10.1006/abbi.2000.1742
Apte RS, Chen DS, Ferrara N (2019) VEGF in signaling and disease: beyond discovery and development. Cell 176(6):1248–1264. https://doi.org/10.1016/j.cell.2019.01.021
Aroor AR, DeMarco VG (2014) Oxidative stress and obesity: the chicken or the egg? Diabetes 63(7):2216–2218. https://doi.org/10.2337/db14-0424
Auvichayapat P, Prapochanung M, Tunkamnerdthai O, Sripanidkulchai BO, Auvichayapat N, Thinkhamrop B, Kunhasura S, Wongpratoom S, Sinawat S, Hongprapas P (2008) Effectiveness of green tea on weight reduction in obese Thais: a randomized, controlled trial. Physiol Behav 93(3):486–491. https://doi.org/10.1016/j.physbeh.2007.10.009
Bae J, Kim N, Shin Y, Kim S-Y, Kim Y-J (2020) Activity of catechins and their applications. Biomed Dermatol 4(1):8. https://doi.org/10.1186/s41702-020-0057-8
Balentine DA, Wiseman SA, Bouwens LC (1997) The chemistry of tea flavonoids. Crit Rev Food Sci Nutr 37(8):693–704. https://doi.org/10.1080/10408399709527797
Berindan-Neagoe I, Braicu C, Irimie A (2012) Combining the chemotherapeutic effects of epigallocatechin 3-gallate with siRNA-mediated p53 knock-down results in synergic pro-apoptotic effects. Int J Nanomedicine 7:6035–6047. https://doi.org/10.2147/IJN.S36523
Biswas SK (2016) Does the interdependence between oxidative stress and inflammation explain the antioxidant paradox? Oxid Med Cell Longev 2016:5698931. https://doi.org/10.1155/2016/5698931
Bloise E, Ortiga-Carvalho TM, Reis FM, Lye SJ, Gibb W, Matthews SG (2016) ATP-binding cassette transporters in reproduction: a new frontier. Hum Reprod Update 22(2):164–181. https://doi.org/10.1093/humupd/dmv049
Braicu C, Gherman CD, Irimie A, Berindan-Neagoe I (2013) Epigallocatechin-3-Gallate (EGCG) inhibits cell proliferation and migratory behaviour of triple negative breast cancer cells. J Nanosci Nanotechnol 13(1):632–637. https://doi.org/10.1166/jnn.2013.6882
Braicu C, Pilecki V, Balacescu O, Irimie A, Neagoe IB (2011) The relationships between biological activities and structure of flavan-3-ols. Int J Mol Sci 12(12):9342–9353. https://doi.org/10.3390/ijms12129342
Bukowski K, Kciuk M, Kontek R (2020) Mechanisms of multidrug resistance in cancer chemotherapy. Int J Mol Sci 21:9. https://doi.org/10.3390/ijms21093233
Cao J, Han J, Xiao H, Qiao J, Han M (2016) Effect of tea polyphenol compounds on anticancer drugs in terms of anti-tumor activity, toxicology, and pharmacokinetics. Nutrients 8:12. https://doi.org/10.3390/nu8120762
Chen H, Landen CN, Li Y, Alvarez RD, Tollefsbol TO (2013a) Enhancement of cisplatin-mediated apoptosis in ovarian cancer cells through potentiating G2/M arrest and p21 upregulation by combinatorial epigallocatechin Gallate and Sulforaphane. J Oncol 2013:872957. https://doi.org/10.1155/2013/872957
Chen H, Landen CN, Li Y, Alvarez RD, Tollefsbol TO (2013b) Epigallocatechin gallate and sulforaphane combination treatment induce apoptosis in paclitaxel-resistant ovarian cancer cells through hTERT and Bcl-2 down-regulation. Exp Cell Res 319(5):697–706. https://doi.org/10.1016/j.yexcr.2012.12.026
Chen J (2016) The cell-cycle arrest and apoptotic functions of p53 in tumor initiation and progression. Cold Spring Harb Perspect Med 6(3):a026104. https://doi.org/10.1101/cshperspect.a026104
Chen JJ, Ye ZQ, Koo MW (2004) Growth inhibition and cell cycle arrest effects of epigallocatechin gallate in the NBT-II bladder tumour cell line. BJU Int 93(7):1082–1086. https://doi.org/10.1111/j.1464-410X.2004.04785.x
Cheng M, Zhang X, Miao Y, Cao J, Wu Z, Weng P (2017) The modulatory effect of (−)-epigallocatechin 3-O-(3-O-methyl) gallate (EGCG3''Me) on intestinal microbiota of high fat diet-induced obesity mice model. Food Res Int 92:9–16. https://doi.org/10.1016/j.foodres.2016.12.008
Chipuk JE, Green DR (2005) Do inducers of apoptosis trigger caspase-independent cell death? Nat Rev Mol Cell Biol 6(3):268–275. https://doi.org/10.1038/nrm2239
Choe SS, Huh JY, Hwang IJ, Kim JI, Kim JB (2016) Adipose tissue remodeling: its role in energy metabolism and metabolic disorders. Front Endocrinol (Lausanne) 7:30. https://doi.org/10.3389/fendo.2016.00030
Cichello S, Liu P, Jois M (2013) The anti-obesity effects of EGCG in relation to oxidative stress and air-pollution in China. Nat Prod Bioprospect 3(6):256–266. https://doi.org/10.1007/s13659-013-0060-5
Colomer R, Sarrats A, Lupu R, Puig T (2017) Natural polyphenols and their synthetic analogs as emerging anticancer agents. Curr Drug Targets 18(2):147–159. https://doi.org/10.2174/1389450117666160112113930
Cowherd RM, Lyle RE, McGehee RE Jr (1999) Molecular regulation of adipocyte differentiation. Semin Cell Dev Biol 10(1):3–10. https://doi.org/10.1006/scdb.1998.0276
de Ferranti S, Mozaffarian D (2008) The perfect storm: obesity, adipocyte dysfunction, and metabolic consequences. Clin Chem 54(6):945–955. https://doi.org/10.1373/clinchem.2007.100156
Deng Y, Scherer PE (2010) Adipokines as novel biomarkers and regulators of the metabolic syndrome. Ann N Y Acad Sci 1212:E1–E19. https://doi.org/10.1111/j.1749-6632.2010.05875.x
Diepvens K, Kovacs EM, Nijs IM, Vogels N, Westerterp-Plantenga MS (2005) Effect of green tea on resting energy expenditure and substrate oxidation during weight loss in overweight females. Br J Nutr 94(6):1026–1034. https://doi.org/10.1079/bjn20051580
Du GJ, Zhang Z, Wen XD, Yu C, Calway T, Yuan CS, Wang CZ (2012) Epigallocatechin Gallate (EGCG) is the most effective cancer chemopreventive polyphenol in green tea. Nutrients 4(11):1679–1691. https://doi.org/10.3390/nu4111679
Farabegoli F, Papi A, Bartolini G, Ostan R, Orlandi M (2010) (−)-Epigallocatechin-3-gallate downregulates Pg-P and BCRP in a tamoxifen resistant MCF-7 cell line. Phytomedicine 17(5):356–362. https://doi.org/10.1016/j.phymed.2010.01.001
Fernandes RC, Araujo VA, Giglio BM, Marini ACB, Mota JF, Teixeira KS, Monteiro PA, Lira FS, Pimentel GD (2018) Acute epigallocatechin 3 Gallate (EGCG) supplementation delays gastric emptying in healthy women: a randomized, double-blind, placebo-controlled crossover study. Nutrients 10:8. https://doi.org/10.3390/nu10081122
Fouad YA, Aanei C (2017) Revisiting the hallmarks of cancer. Am J Cancer Res 7(5):1016–1036
Friedrich M, Petzke KJ, Raederstorff D, Wolfram S, Klaus S (2012) Acute effects of epigallocatechin gallate from green tea on oxidation and tissue incorporation of dietary lipids in mice fed a high-fat diet. Int J Obes (Lond) 36(5):735–743. https://doi.org/10.1038/ijo.2011.136
Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, Nakajima Y, Nakayama O, Makishima M, Matsuda M, Shimomura I (2004) Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest 114(12):1752–1761. https://doi.org/10.1172/JCI21625
Furuyashiki T, Nagayasu H, Aoki Y, Bessho H, Hashimoto T, Kanazawa K, Ashida H (2004) Tea catechin suppresses adipocyte differentiation accompanied by down-regulation of PPARgamma2 and C/EBPalpha in 3T3-L1 cells. Biosci Biotechnol Biochem 68(11):2353–2359. https://doi.org/10.1271/bbb.68.2353
Gao CL, Zhu C, Zhao YP, Chen XH, Ji CB, Zhang CM, Zhu JG, Xia ZK, Tong ML, Guo XR (2010) Mitochondrial dysfunction is induced by high levels of glucose and free fatty acids in 3T3-L1 adipocytes. Mol Cell Endocrinol 320(1–2):25–33. https://doi.org/10.1016/j.mce.2010.01.039
Grove KA, Sae-tan S, Kennett MJ, Lambert JD (2012) (−)-Epigallocatechin-3-gallate inhibits pancreatic lipase and reduces body weight gain in high fat-fed obese mice. Obesity (Silver Spring) 20(11):2311–2313. https://doi.org/10.1038/oby.2011.139
Gupta S, Hussain T, Mukhtar H (2003) Molecular pathway for (−)-epigallocatechin-3-gallate-induced cell cycle arrest and apoptosis of human prostate carcinoma cells. Arch Biochem Biophys 410(1):177–185. https://doi.org/10.1016/s0003-9861(02)00668-9
Hamed AR, Abdel-Azim NS, Shams KA, Hammouda FM (2019) Targeting multidrug resistance in cancer by natural chemosensitizers. Bull Natl Res Centre 43(1):8. https://doi.org/10.1186/s42269-019-0043-8
Haque A, Rahman MA, Chen ZG, Saba NF, Khuri FR, Shin DM, Ruhul Amin AR (2015) Combination of erlotinib and EGCG induces apoptosis of head and neck cancers through posttranscriptional regulation of Bim and Bcl-2. Apoptosis 20(7):986–995. https://doi.org/10.1007/s10495-015-1126-0
Harakeh S, Abu-El-Ardat K, Diab-Assaf M, Niedzwiecki A, El-Sabban M, Rath M (2008) Epigallocatechin-3-gallate induces apoptosis and cell cycle arrest in HTLV-1-positive and -negative leukemia cells. Med Oncol 25(1):30–39. https://doi.org/10.1007/s12032-007-0036-6
Hastak K, Gupta S, Ahmad N, Agarwal MK, Agarwal ML, Mukhtar H (2003) Role of p53 and NF-kappaB in epigallocatechin-3-gallate-induced apoptosis of LNCaP cells. Oncogene 22(31):4851–4859. https://doi.org/10.1038/sj.onc.1206708
Huang CH, Tsai SJ, Wang YJ, Pan MH, Kao JY, Way TD (2009) EGCG inhibits protein synthesis, lipogenesis, and cell cycle progression through activation of AMPK in p53 positive and negative human hepatoma cells. Mol Nutr Food Res 53(9):1156–1165. https://doi.org/10.1002/mnfr.200800592
Huang H (2018) Matrix Metalloproteinase-9 (MMP-9) as a cancer biomarker and MMP-9 biosensors: recent advances. Sensors (Basel) 18:10. https://doi.org/10.3390/s18103249
Huang J, Wang Y, Xie Z, Zhou Y, Zhang Y, Wan X (2014) The anti-obesity effects of green tea in human intervention and basic molecular studies. Eur J Clin Nutr 68(10):1075–1087. https://doi.org/10.1038/ejcn.2014.143
Huang J, Zhang Y, Zhou Y, Zhang Z, Xie Z, Zhang J, Wan X (2013) Green tea polyphenols alleviate obesity in broiler chickens through the regulation of lipid-metabolism-related genes and transcription factor expression. J Agric Food Chem 61(36):8565–8572. https://doi.org/10.1021/jf402004x
Huang JB, Zhang Y, Zhou YB, Wan XC, Zhang JS (2015) Effects of epigallocatechin gallate on lipid metabolism and its underlying molecular mechanism in broiler chickens. J Anim Physiol Anim Nutr (Berl) 99(4):719–727. https://doi.org/10.1111/jpn.12276
Hwang JT, Park IJ, Shin JI, Lee YK, Lee SK, Baik HW, Ha J, Park OJ (2005) Genistein, EGCG, and capsaicin inhibit adipocyte differentiation process via activating AMP-activated protein kinase. Biochem Biophys Res Commun 338(2):694–699. https://doi.org/10.1016/j.bbrc.2005.09.195
Hwang YS, Park KK, Chung WY (2013) Epigallocatechin-3 gallate inhibits cancer invasion by repressing functional invadopodia formation in oral squamous cell carcinoma. Eur J Pharmacol 715(1–3):286–295. https://doi.org/10.1016/j.ejphar.2013.05.008
Ikeda I, Tsuda K, Suzuki Y, Kobayashi M, Unno T, Tomoyori H, Goto H, Kawata Y, Imaizumi K, Nozawa A, Kakuda T (2005) Tea catechins with a galloyl moiety suppress postprandial hypertriacylglycerolemia by delaying lymphatic transport of dietary fat in rats. J Nutr 135(2):155–159. https://doi.org/10.1093/jn/135.2.155
Jiang WG, Sanders AJ, Katoh M, Ungefroren H, Gieseler F, Prince M, Thompson SK, Zollo M, Spano D, Dhawan P, Sliva D, Subbarayan PR, Sarkar M, Honoki K, Fujii H, Georgakilas AG, Amedei A, Niccolai E, Amin A, Ashraf SS, Ye L, Helferich WG, Yang X, Boosani CS, Guha G, Ciriolo MR, Aquilano K, Chen S, Azmi AS, Keith WN, Bilsland A, Bhakta D, Halicka D, Nowsheen S, Pantano F, Santini D (2015) Tissue invasion and metastasis: molecular, biological and clinical perspectives. Semin Cancer Biol 35(Suppl):S244–S275. https://doi.org/10.1016/j.semcancer.2015.03.008
Jin L, Li C, Xu Y, Wang L, Liu J, Wang D, Hong C, Jiang Z, Ma Y, Chen Q, Yu F (2013) Epigallocatechin gallate promotes p53 accumulation and activity via the inhibition of MDM2-mediated p53 ubiquitination in human lung cancer cells. Oncol Rep 29(5):1983–1990. https://doi.org/10.3892/or.2013.2343
Josic J, Olsson AT, Wickeberg J, Lindstedt S, Hlebowicz J (2010) Does green tea affect postprandial glucose, insulin and satiety in healthy subjects: a randomized controlled trial. Nutr J 9:63. https://doi.org/10.1186/1475-2891-9-63
Jung YD, Kim MS, Shin BA, Chay KO, Ahn BW, Liu W, Bucana CD, Gallick GE, Ellis LM (2001) EGCG, a major component of green tea, inhibits tumour growth by inhibiting VEGF induction in human colon carcinoma cells. Br J Cancer 84(6):844–850. https://doi.org/10.1054/bjoc.2000.1691
Kang SU, Lee BS, Lee SH, Baek SJ, Shin YS, Kim CH (2013) Expression of NSAID-activated gene-1 by EGCG in head and neck cancer: involvement of ATM-dependent p53 expression. J Nutr Biochem 24(6):986–999. https://doi.org/10.1016/j.jnutbio.2012.07.003
Kao YH, Hiipakka RA, Liao S (2000) Modulation of obesity by a green tea catechin. Am J Clin Nutr 72(5):1232–1234. https://doi.org/10.1093/ajcn/72.5.1232
Kaufmann R, Henklein P, Henklein P, Settmacher U (2009) Green tea polyphenol epigallocatechin-3-gallate inhibits thrombin-induced hepatocellular carcinoma cell invasion and p42/p44-MAPKinase activation. Oncol Rep 21(5):1261–1267. https://doi.org/10.3892/or_00000349
Khan N, Mukhtar H (2007) Tea polyphenols for health promotion. Life Sci 81(7):519–533. https://doi.org/10.1016/j.lfs.2007.06.011
Kim GW, Lin JE, Valentino MA, Colon-Gonzalez F, Waldman SA (2011) Regulation of appetite to treat obesity. Expert Rev Clin Pharmacol 4(2):243–259. https://doi.org/10.1586/ecp.11.3
Koh YW, Choi EC, Kang SU, Hwang HS, Lee MH, Pyun J, Park R, Lee Y, Kim CH (2011) Green tea (−)-epigallocatechin-3-gallate inhibits HGF-induced progression in oral cavity cancer through suppression of HGF/c-Met. J Nutr Biochem 22(11):1074–1083. https://doi.org/10.1016/j.jnutbio.2010.09.005
Kushima Y, Iida K, Nagaoka Y, Kawaratani Y, Shirahama T, Sakaguchi M, Baba K, Hara Y, Uesato S (2009) Inhibitory effect of (−)-epigallocatechin and (−)-epigallocatechin gallate against heregulin beta1-induced migration/invasion of the MCF-7 breast carcinoma cell line. Biol Pharm Bull 32(5):899–904. https://doi.org/10.1248/bpb.32.899
Kwak IH, Shin YH, Kim M, Cha HY, Nam HJ, Lee BS, Chaudhary SC, Pai KS, Lee JH (2011) Epigallocatechin-3-gallate inhibits paracrine and autocrine hepatocyte growth factor/scatter factor-induced tumor cell migration and invasion. Exp Mol Med 43(2):111–120. https://doi.org/10.3858/emm.2011.43.2.013
Lecumberri E, Dupertuis YM, Miralbell R, Pichard C (2013) Green tea polyphenol epigallocatechin-3-gallate (EGCG) as adjuvant in cancer therapy. Clin Nutr 32(6):894–903. https://doi.org/10.1016/j.clnu.2013.03.008
Lee H, Bae S, Yoon Y (2013) The anti-adipogenic effects of (−)epigallocatechin gallate are dependent on the WNT/beta-catenin pathway. J Nutr Biochem 24(7):1232–1240. https://doi.org/10.1016/j.jnutbio.2012.09.007
Lee JH, Jeong YJ, Lee SW, Kim D, Oh SJ, Lim HS, Oh HK, Kim SH, Kim WJ, Jung JY (2010) EGCG induces apoptosis in human laryngeal epidermoid carcinoma Hep2 cells via mitochondria with the release of apoptosis-inducing factor and endonuclease G. Cancer Lett 290(1):68–75. https://doi.org/10.1016/j.canlet.2009.08.027
Legeay S, Rodier M, Fillon L, Faure S, Clere N (2015) Epigallocatechin Gallate: a review of its beneficial properties to prevent metabolic syndrome. Nutrients 7(7):5443–5468. https://doi.org/10.3390/nu7075230
Li F, Gao C, Yan P, Zhang M, Wang Y, Hu Y, Wu X, Wang X, Sheng J (2018) EGCG reduces obesity and white adipose tissue gain partly through AMPK activation in mice. Front Pharmacol 9:1366. https://doi.org/10.3389/fphar.2018.01366
Li Y, Zhao S, Zhang W, Zhao P, He B, Wu N, Han P (2011) Epigallocatechin-3-O-gallate (EGCG) attenuates FFAs-induced peripheral insulin resistance through AMPK pathway and insulin signaling pathway in vivo. Diabetes Res Clin Pract 93(2):205–214. https://doi.org/10.1016/j.diabres.2011.03.036
Liguori I, Russo G, Curcio F, Bulli G, Aran L, Della-Morte D, Gargiulo G, Testa G, Cacciatore F, Bonaduce D, Abete P (2018) Oxidative stress, aging, and diseases. Clin Interv Aging 13:757–772. https://doi.org/10.2147/CIA.S158513
Lim YC, Park HY, Hwang HS, Kang SU, Pyun JH, Lee MH, Choi EC, Kim CH (2008) (−)-Epigallocatechin-3-gallate (EGCG) inhibits HGF-induced invasion and metastasis in hypopharyngeal carcinoma cells. Cancer Lett 271(1):140–152. https://doi.org/10.1016/j.canlet.2008.05.048
Lin J, Della-Fera MA, Baile CA (2005) Green tea polyphenol epigallocatechin gallate inhibits adipogenesis and induces apoptosis in 3T3-L1 adipocytes. Obes Res 13(6):982–990. https://doi.org/10.1038/oby.2005.115
Liu S, Wang XJ, Liu Y, Cui YF (2013) PI3K/AKT/mTOR signaling is involved in (−)-epigallocatechin-3-gallate-induced apoptosis of human pancreatic carcinoma cells. Am J Chin Med 41(3):629–642. https://doi.org/10.1142/S0192415X13500444
Lobo V, Patil A, Phatak A, Chandra N (2010) Free radicals, antioxidants and functional foods: impact on human health. Pharmacogn Rev 4(8):118–126. https://doi.org/10.4103/0973-7847.70902
MacLean PS, Blundell JE, Mennella JA, Batterham RL (2017) Biological control of appetite: a daunting complexity. Obesity (Silver Spring) 25:8–16. https://doi.org/10.1002/oby.21771
Mahmood N, Mihalcioiu C, Rabbani SA (2018) Multifaceted role of the Urokinase-type plasminogen activator (uPA) and its receptor (uPAR): diagnostic, prognostic, and therapeutic applications. Front Oncol 8:24. https://doi.org/10.3389/fonc.2018.00024
Mangine GT, Gonzalez AM, Wells AJ, McCormack WP, Fragala MS, Stout JR, Hoffman JR (2012) The effect of a dietary supplement (N-oleyl-phosphatidyl-ethanolamine and epigallocatechin gallate) on dietary compliance and body fat loss in adults who are overweight: a double-blind, randomized control trial. Lipids Health Dis 11:127. https://doi.org/10.1186/1476-511X-11-127
Manna P, Jain SK (2015) Obesity, oxidative stress, adipose tissue dysfunction, and the associated health risks: causes and therapeutic strategies. Metab Syndr Relat Disord 13(10):423–444. https://doi.org/10.1089/met.2015.0095
Marseglia L, Manti S, D'Angelo G, Nicotera A, Parisi E, Di Rosa G, Gitto E, Arrigo T (2014) Oxidative stress in obesity: a critical component in human diseases. Int J Mol Sci 16(1):378–400. https://doi.org/10.3390/ijms16010378
Masuda M, Suzui M, Weinstein IB (2001) Effects of epigallocatechin-3-gallate on growth, epidermal growth factor receptor signaling pathways, gene expression, and chemosensitivity in human head and neck squamous cell carcinoma cell lines. Clin Cancer Res 7(12):4220–4229
Matsuda M, Shimomura I (2013) Increased oxidative stress in obesity: implications for metabolic syndrome, diabetes, hypertension, dyslipidemia, atherosclerosis, and cancer. Obes Res Clin Pract 7(5):e330–e341. https://doi.org/10.1016/j.orcp.2013.05.004
Mayr C, Wagner A, Neureiter D, Pichler M, Jakab M, Illig R, Berr F, Kiesslich T (2015) The green tea catechin epigallocatechin gallate induces cell cycle arrest and shows potential synergism with cisplatin in biliary tract cancer cells. BMC Complement Altern Med 15:194. https://doi.org/10.1186/s12906-015-0721-5
Meirson T, Gil-Henn H, Samson AO (2020) Invasion and metastasis: the elusive hallmark of cancer. Oncogene 39(9):2024–2026. https://doi.org/10.1038/s41388-019-1110-1
Mittal M, Siddiqui MR, Tran K, Reddy SP, Malik AB (2014) Reactive oxygen species in inflammation and tissue injury. Antioxid Redox Signal 20(7):1126–1167. https://doi.org/10.1089/ars.2012.5149
Mohan N, Karmakar S, Banik NL, Ray SK (2011) SU5416 and EGCG work synergistically and inhibit angiogenic and survival factors and induce cell cycle arrest to promote apoptosis in human malignant neuroblastoma SH-SY5Y and SK-N-BE2 cells. Neurochem Res 36(8):1383–1396. https://doi.org/10.1007/s11064-011-0463-9
Momose Y, Maeda-Yamamoto M, Nabetani H (2016) Systematic review of green tea epigallocatechin gallate in reducing low-density lipoprotein cholesterol levels of humans. Int J Food Sci Nutr 67(6):606–613. https://doi.org/10.1080/09637486.2016.1196655
Moore RJ, Jackson KG, Minihane AM (2009) Green tea (Camellia sinensis) catechins and vascular function. Br J Nutr 102(12):1790–1802. https://doi.org/10.1017/S0007114509991218
Mukhtar H, Ahmad N (2000) Tea polyphenols: prevention of cancer and optimizing health. Am J Clin Nutr 71(6 Suppl):1698–1702. https://doi.org/10.1093/ajcn/71.6.1698S
Nagao T, Hase T, Tokimitsu I (2007) A green tea extract high in catechins reduces body fat and cardiovascular risks in humans. Obesity (Silver Spring) 15(6):1473–1483. https://doi.org/10.1038/oby.2007.176
Negri A, Naponelli V, Rizzi F, Bettuzzi S (2018) Molecular targets of epigallocatechin-Gallate (EGCG): a special focus on signal transduction and cancer. Nutrients 10:12. https://doi.org/10.3390/nu10121936
Nihal M, Roelke CT, Wood GS (2010) Anti-melanoma effects of vorinostat in combination with polyphenolic antioxidant (−)-epigallocatechin-3-gallate (EGCG). Pharm Res 27(6):1103–1114. https://doi.org/10.1007/s11095-010-0054-5
Nikoo M, Regenstein JM, Gavlighi HA (2018) Antioxidant and antimicrobial activities of (−)-Epigallocatechin-3-gallate (EGCG) and its potential to preserve the quality and safety of foods. Compr Rev Food Sci Food Saf 17(3):732–753
Nishida N, Yano H, Nishida T, Kamura T, Kojiro M (2006) Angiogenesis in cancer. Vasc Health Risk Manag 2(3):213–219. https://doi.org/10.2147/vhrm.2006.2.3.213
Nishikawa T, Nakajima T, Moriguchi M, Jo M, Sekoguchi S, Ishii M, Takashima H, Katagishi T, Kimura H, Minami M, Itoh Y, Kagawa K, Okanoue T (2006) A green tea polyphenol, epigalocatechin-3-gallate, induces apoptosis of human hepatocellular carcinoma, possibly through inhibition of Bcl-2 family proteins. J Hepatol 44(6):1074–1082. https://doi.org/10.1016/j.jhep.2005.11.045
Nurgali K, Jagoe RT, Abalo R (2018) Editorial: adverse effects of cancer chemotherapy: anything new to improve tolerance and reduce sequelae? Front Pharmacol 9:245. https://doi.org/10.3389/fphar.2018.00245
Park HJ, DiNatale DA, Chung MY, Park YK, Lee JY, Koo SI, O'Connor M, Manautou JE, Bruno RS (2011) Green tea extract attenuates hepatic steatosis by decreasing adipose lipogenesis and enhancing hepatic antioxidant defenses in Ob/Ob mice. J Nutr Biochem 22(4):393–400. https://doi.org/10.1016/j.jnutbio.2010.03.009
Patel MS, Owen OE, Goldman LI, Hanson RW (1975) Fatty acid synthesis by human adipose tissue. Metabolism 24(2):161–173. https://doi.org/10.1016/0026-0495(75)90017-7
Pilorget A, Berthet V, Luis J, Moghrabi A, Annabi B, Beliveau R (2003) Medulloblastoma cell invasion is inhibited by green tea (−)epigallocatechin-3-gallate. J Cell Biochem 90(4):745–755. https://doi.org/10.1002/jcb.10667
Przystupski D, Michel O, Rossowska J, Kwiatkowski S, Saczko J, Kulbacka J (2019) The modulatory effect of green tea catechin on drug resistance in human ovarian cancer cells. Med Chem Res 28(5):657–667. https://doi.org/10.1007/s00044-019-02324-6
Qiao J, Gu C, Shang W, Du J, Yin W, Zhu M, Wang W, Han M, Lu W (2011) Effect of green tea on pharmacokinetics of 5-fluorouracil in rats and pharmacodynamics in human cell lines in vitro. Food Chem Toxicol 49(6):1410–1415. https://doi.org/10.1016/j.fct.2011.03.033
Qin J, Xie LP, Zheng XY, Wang YB, Bai Y, Shen HF, Li LC, Dahiya R (2007) A component of green tea, (−)-epigallocatechin-3-gallate, promotes apoptosis in T24 human bladder cancer cells via modulation of the PI3K/Akt pathway and Bcl-2 family proteins. Biochem Biophys Res Commun 354(4):852–857. https://doi.org/10.1016/j.bbrc.2007.01.003
Raederstorff DG, Schlachter MF, Elste V, Weber P (2003) Effect of EGCG on lipid absorption and plasma lipid levels in rats. J Nutr Biochem 14(6):326–332. https://doi.org/10.1016/s0955-2863(03)00054-8
Rains TM, Agarwal S, Maki KC (2011) Antiobesity effects of green tea catechins: a mechanistic review. J Nutr Biochem 22(1):1–7. https://doi.org/10.1016/j.jnutbio.2010.06.006
Rayan A, Raiyn J, Falah M (2017) Nature is the best source of anticancer drugs: indexing natural products for their anticancer bioactivity. PLoS One 12(11):e0187925. https://doi.org/10.1371/journal.pone.0187925
Reinbach HC, Smeets A, Martinussen T, Moller P, Westerterp-Plantenga MS (2009) Effects of capsaicin, green tea and CH-19 sweet pepper on appetite and energy intake in humans in negative and positive energy balance. Clin Nutr 28(3):260–265. https://doi.org/10.1016/j.clnu.2009.01.010
Roberto CA, Swinburn B, Hawkes C, Huang TT, Costa SA, Ashe M, Zwicker L, Cawley JH, Brownell KD (2015) Patchy progress on obesity prevention: emerging examples, entrenched barriers, and new thinking. Lancet 385(9985):2400–2409. https://doi.org/10.1016/S0140-6736(14)61744-X
Rondanelli M, Opizzi A, Solerte SB, Trotti R, Klersy C, Cazzola R (2009) Administration of a dietary supplement ( N-oleyl-phosphatidylethanolamine and epigallocatechin-3-gallate formula) enhances compliance with diet in healthy overweight subjects: a randomized controlled trial. Br J Nutr 101(3):457–464. https://doi.org/10.1017/S0007114508024008
Roy AM, Baliga MS, Katiyar SK (2005) Epigallocatechin-3-gallate induces apoptosis in estrogen receptor-negative human breast carcinoma cells via modulation in protein expression of p53 and Bax and caspase-3 activation. Mol Cancer Ther 4(1):81–90
Sae-Tan S, Grove KA, Kennett MJ, Lambert JD (2011) (−)-Epigallocatechin-3-gallate increases the expression of genes related to fat oxidation in the skeletal muscle of high fat-fed mice. Food Funct 2(2):111–116. https://doi.org/10.1039/c0fo00155d
Samavat H, Newman AR, Wang R, Yuan JM, Wu AH, Kurzer MS (2016) Effects of green tea catechin extract on serum lipids in postmenopausal women: a randomized, placebo-controlled clinical trial. Am J Clin Nutr 104(6):1671–1682. https://doi.org/10.3945/ajcn.116.137075
Senanayake SN (2013) Green tea extract: chemistry, antioxidant properties and food applications—a review. J Funct Foods 5(4):1529–1541
Shankar S, Marsh L, Srivastava RK (2013) EGCG inhibits growth of human pancreatic tumors orthotopically implanted in Balb C nude mice through modulation of FKHRL1/FOXO3a and neuropilin. Mol Cell Biochem 372(1–2):83–94. https://doi.org/10.1007/s11010-012-1448-y
Shen X, Zhang Y, Feng Y, Zhang L, Li J, Xie YA, Luo X (2014) Epigallocatechin-3-gallate inhibits cell growth, induces apoptosis and causes S phase arrest in hepatocellular carcinoma by suppressing the AKT pathway. Int J Oncol 44(3):791–796. https://doi.org/10.3892/ijo.2014.2251
Shimizu M, Shirakami Y, Sakai H, Yasuda Y, Kubota M, Adachi S, Tsurumi H, Hara Y, Moriwaki H (2010) (−)-epigallocatechin gallate inhibits growth and activation of the VEGF/VEGFR axis in human colorectal cancer cells. Chem Biol Interact 185(3):247–252. https://doi.org/10.1016/j.cbi.2010.03.036
Singh BN, Shankar S, Srivastava RK (2011) Green tea catechin, epigallocatechin-3-gallate (EGCG): mechanisms, perspectives and clinical applications. Biochem Pharmacol 82(12):1807–1821. https://doi.org/10.1016/j.bcp.2011.07.093
Smith J, Al-Amri M, Dorairaj P, Sniderman A (2006) The adipocyte life cycle hypothesis. Clin Sci (Lond) 110(1):1–9. https://doi.org/10.1042/CS20050110
Stamenkovic I (2000) Matrix metalloproteinases in tumor invasion and metastasis. Semin Cancer Biol 10(6):415–433. https://doi.org/10.1006/scbi.2000.0379
Stearns ME, Wang M (2011) Synergistic effects of the Green tea extract Epigallocatechin-3-gallate and Taxane in eradication of malignant human prostate tumors. Transl Oncol 4(3):147–156. https://doi.org/10.1593/tlo.10286
Suganuma M, Okabe S, Oniyama M, Tada Y, Ito H, Fujiki H (1998) Wide distribution of [3H](−)-epigallocatechin gallate, a cancer preventive tea polyphenol, in mouse tissue. Carcinogenesis 19(10):1771–1776. https://doi.org/10.1093/carcin/19.10.1771
Suliburska J, Bogdanski P, Szulinska M, Stepien M, Pupek-Musialik D, Jablecka A (2012) Effects of green tea supplementation on elements, total antioxidants, lipids, and glucose values in the serum of obese patients. Biol Trace Elem Res 149(3):315–322. https://doi.org/10.1007/s12011-012-9448-z
Tauber AL, Schweiker SS, Levonis SM (2020) From tea to treatment; epigallocatechin gallate and its potential involvement in minimizing the metabolic changes in cancer. Nutr Res 74:23–36. https://doi.org/10.1016/j.nutres.2019.12.004
Thakur VS, Gupta K, Gupta S (2012) Green tea polyphenols increase p53 transcriptional activity and acetylation by suppressing class I histone deacetylases. Int J Oncol 41(1):353–361. https://doi.org/10.3892/ijo.2012.1449
Timper K, Bruning JC (2017) Hypothalamic circuits regulating appetite and energy homeostasis: pathways to obesity. Dis Model Mech 10(6):679–689. https://doi.org/10.1242/dmm.026609
Tran PL, Kim SA, Choi HS, Yoon JH, Ahn SG (2010) Epigallocatechin-3-gallate suppresses the expression of HSP70 and HSP90 and exhibits anti-tumor activity in vitro and in vivo. BMC Cancer 10:276. https://doi.org/10.1186/1471-2407-10-276
Tsai M-C, Yen Y-H, Chang K-C, Hung C-H, Chen C-H, Lin M-T, Hu T-H (2019) Elevated levels of serum urokinase plasminogen activator predict poor prognosis in hepatocellular carcinoma after resection. BMC Cancer 19(1):1169. https://doi.org/10.1186/s12885-019-6397-3
Tsao R (2010) Chemistry and biochemistry of dietary polyphenols. Nutrients 2(12):1231–1246. https://doi.org/10.3390/nu2121231
Valcic S, Muders A, Jacobsen NE, Liebler DC, Timmermann BN (1999) Antioxidant chemistry of green tea catechins. Identification of products of the reaction of (−)-epigallocatechin gallate with peroxyl radicals. Chem Res Toxicol 12(4):382–386. https://doi.org/10.1021/tx990003t
Vincent HK, Taylor AG (2006) Biomarkers and potential mechanisms of obesity-induced oxidant stress in humans. Int J Obes (Lond) 30(3):400–418. https://doi.org/10.1038/sj.ijo.0803177
Wang S, Sun Z, Dong S, Liu Y, Liu Y (2014) Molecular interactions between (−)-epigallocatechin gallate analogs and pancreatic lipase. PLoS One 9(11):e111143. https://doi.org/10.1371/journal.pone.0111143
Wang X, Baek SJ, Eling TE (2013) The diverse roles of nonsteroidal anti-inflammatory drug activated gene (NAG-1/GDF15) in cancer. Biochem Pharmacol 85(5):597–606. https://doi.org/10.1016/j.bcp.2012.11.025
Wang X, Jiang P, Wang P, Yang CS, Wang X, Feng Q (2015) EGCG enhances cisplatin sensitivity by regulating expression of the copper and cisplatin influx transporter CTR1 in ovary cancer. PLoS One 10(4):e0125402. https://doi.org/10.1371/journal.pone.0125402
Westerterp-Plantenga MS, Lejeune MP, Kovacs EM (2005) Body weight loss and weight maintenance in relation to habitual caffeine intake and green tea supplementation. Obes Res 13(7):1195–1204. https://doi.org/10.1038/oby.2005.142
Wu BT, Hung PF, Chen HC, Huang RN, Chang HH, Kao YH (2005) The apoptotic effect of green tea (−)-epigallocatechin gallate on 3T3-L1 preadipocytes depends on the Cdk2 pathway. J Agric Food Chem 53(14):5695–5701. https://doi.org/10.1021/jf050045p
Wu Z, Rosen ED, Brun R, Hauser S, Adelmant G, Troy AE, McKeon C, Darlington GJ, Spiegelman BM (1999) Cross-regulation of C/EBP alpha and PPAR gamma controls the transcriptional pathway of adipogenesis and insulin sensitivity. Mol Cell 3(2):151–158. https://doi.org/10.1016/s1097-2765(00)80306-8
Yang S, Zhao X, Xu H, Chen F, Xu Y, Li Z, Sanchis D, Jin L, Zhang Y, Ye J (2017) AKT2 blocks nucleus translocation of apoptosis-inducing factor (AIF) and endonuclease G (EndoG) while promoting caspase activation during cardiac ischemia. Int J Mol Sci 18:3. https://doi.org/10.3390/ijms18030565
Yuan CH, Horng CT, Lee CF, Chiang NN, Tsai FJ, Lu CC, Chiang JH, Hsu YM, Yang JS, Chen FA (2017) Epigallocatechin gallate sensitizes cisplatin-resistant oral cancer CAR cell apoptosis and autophagy through stimulating AKT/STAT3 pathway and suppressing multidrug resistance 1 signaling. Environ Toxicol 32(3):845–855. https://doi.org/10.1002/tox.22284
Zhang Y, Duan W, Owusu L, Wu D, Xin Y (2015) Epigallocatechin-3-gallate induces the apoptosis of hepatocellular carcinoma LM6 cells but not non-cancerous liver cells. Int J Mol Med 35(1):117–124. https://doi.org/10.3892/ijmm.2014.1988
Zhang Y, Han G, Fan B, Zhou Y, Zhou X, Wei L, Zhang J (2009) Green tea (−)-epigallocatechin-3-gallate down-regulates VASP expression and inhibits breast cancer cell migration and invasion by attenuating Rac1 activity. Eur J Pharmacol 606(1–3):172–179. https://doi.org/10.1016/j.ejphar.2008.12.033
Zhao X, Guan JL (2011) Focal adhesion kinase and its signaling pathways in cell migration and angiogenesis. Adv Drug Deliv Rev 63(8):610–615. https://doi.org/10.1016/j.addr.2010.11.001
Zhao Y, Yang LF, Ye M, Gu HH, Cao Y (2004) Induction of apoptosis by epigallocatechin-3-gallate via mitochondrial signal transduction pathway. Prev Med 39(6):1172–1179. https://doi.org/10.1016/j.ypmed.2004.04.042
Zhu BH, Chen HY, Zhan WH, Wang CY, Cai SR, Wang Z, Zhang CH, He YL (2011) (−)-Epigallocatechin-3-gallate inhibits VEGF expression induced by IL-6 via Stat3 in gastric cancer. World J Gastroenterol 17(18):2315–2325. https://doi.org/10.3748/wjg.v17.i18.2315
Acknowledgments
We thankfully acknowledge fellowship support to Shiv Govind Rawat [Award No. 09/013(0772/2018-EMR-I)] from CSIR, New Delhi. The fellowship supports to Rajan Kumar Tiwari [Award No. R/Dev/IX-Sch.(SRF-JRF-CAS-Zoology)/75159] from University Grants Commission-Career Advancement Scheme (UGC-CAS); Pratishtha Sonker [Award No. F117.1/201516/RGNF201517SCUTT4822/(SAIII/Website)] from University Grants Commission (UGC), New Delhi is highly acknowledged. Funding from the University Grants Commission and Department of Science & Technology, New Delhi, India, in the form of UGC-Start-Up Research (F. No. 30-370/2017 (BSR)) and Early Career Research Award (ECR/2016/001117) is highly acknowledged. Financial support from Interdisciplinary School of Life Science (ISLS) and University Grants Commission-Universities with Potential for Excellence (UGC-UPE), Banaras Hindu University is also acknowledged. We also acknowledge UGC-CAS and DST-FIST program to the Department of Zoology, Banaras Hindu University, India.
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Rawat, S.G., Tiwari, R.K., Sonker, P., Maurya, R.P., Vishvakarma, N.K., Kumar, A. (2021). EGCG as Anti-Obesity and Anticancer Agent. In: Kumar, S., Gupta, S. (eds) Obesity and Cancer. Springer, Singapore. https://doi.org/10.1007/978-981-16-1846-8_11
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