The Possibility of Preventive and Therapeutic Use of Green Tea Catechins in Prostate Cancer

Author(s): Vladimir S. Rogovskii*, Sergey V. Popov, Nikolai V. Sturov, Nikolai L. Shimanovskii

Journal Name: Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Volume 19 , Issue 10 , 2019

Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Background: Prostate cancer is one of the most frequent types of cancer. Despite the existence of various treatment strategies, treatment of prostate cancer still presents serious difficulties (especially in advanced stages). Polyphenols have been extensively assessed in terms of their potential use for prostate cancer treatment and prevention. Catechins are among the most well-known polyphenols in this respect.

Objective: In this review, we summarize clinical study results concerning catechin applications with regard to prostate cancer treatment and prevention. We discuss some of the main mechanisms of the anticarcinogenic action of catechins.

Conclusion: The main mechanisms of the anticarcinogenic action of catechins are subdivided into two major types: (i) direct action on cancer cells and (ii) indirect effect based on catechins’s impact on the microenvironment of cancer cells, particularly in relation to the immune system. At this level catechins might reduce tumor-associated inflammation and immune tolerance.

Keywords: Catechins, polyphenols, cancer, prostate cancer, inflammation, immunity, immune tolerance.

Nam, S.; Smith, D.M.; Dou, Q.P. Ester bond-containing tea polyphenols potently inhibit proteasome activity in vitro and in vivo. J. Biol. Chem., 2001, 276(16), 13322-13330.
Jian, L.; Xie, L.P.; Lee, A.H.; Binns, C.W. Protective effect of green tea against prostate cancer: a case-control study in southeast China. Int. J. Cancer, 2004, 108(1), 130-135.
Hussain, T.; Tan, B.; Yin, Y.; Blachier, F.; Tossou, M.C.; Rahu, N. Oxidative stress and inflammation: What polyphenols can do for us? Oxid. Med. Cell. Longev., 2016, 20167432797
Kiemlian Kwee, J. Yin and Yang of polyphenols in cancer prevention: A short review. Anticancer. Agents Med. Chem., 2016, 16(7), 832-840.
Fedotcheva, T.A.; Matyushin, A.I.; Rzheznikov, V.M.; Shimanovskii, N.L. Antioxidant and cytoprotector properties of genistein - Isoflavone with estrogenic activity. Eksp. Klin. Farmakol., 2016, 79(12), 24-28.
Gupta, S.; Mukhtar, H. Green tea and prostate cancer. Urol. Clin. North Am., 2002, 29(1), 49-57.
Johnson, J.J.; Bailey, H.H.; Mukhtar, H. Green tea polyphenols for prostate cancer chemoprevention: A translational perspective. Phytomedicine, 2010, 17(1), 3-13.
Jowko, E. Green Tea Catechins and Sport Performance.In: Antioxidants in Sport Nutrition; Lamprecht, M., Ed.; CRC Press/Taylor & Francis: Boca Raton, FL, 2015.
Bettuzzi, S.; Brausi, M.; Rizzi, F.; Castagnetti, G.; Peracchia, G.; Corti, A. Chemoprevention of human prostate cancer by oral administration of green tea catechins in volunteers with high-grade prostate intraepithelial neoplasia: A preliminary report from a one-year proof-of-principle study. Cancer Res., 2006, 66(2), 1234-1240.
Cui, K.; Li, X.; Du, Y.; Tang, X.; Arai, S.; Geng, Y.; Xi, Y.; Xu, H.; Zhou, Y.; Ma, W.; Zhang, T. Chemoprevention of prostate cancer in men with high-grade prostatic intraepithelial neoplasia (HGPIN): A systematic review and adjusted indirect treatment comparison. Oncotarget, 2017, 8(22), 36674-36684.
Popov, S.V. Prophylactic use of the drug Indigal in diseases of the prostate. Effect. Pharmacother. Urol. Nephrol., 2008, 4, 42-44.
Jatoi, A.; Ellison, N.; Burch, P.A.; Sloan, J.A.; Dakhil, S.R.; Novotny, P.; Tan, W.; Fitch, T.R.; Rowland, K.M.; Young, C.Y.; Flynn, P.J. A phase II trial of green tea in the treatment of patients with androgen independent metastatic prostate carcinoma. Cancer, 2003, 97(6), 1442-1446.
Choan, E.; Segal, R.; Jonker, D.; Malone, S.; Reaume, N.; Eapen, L.; Gallant, V. A prospective clinical trial of green tea for hormone refractory prostate cancer: An evaluation of the complementary/ alternative therapy approach. Urol. Oncol., 2005, 23(2), 108-113.
McLarty, J.; Bigelow, R.L.; Smith, M.; Elmajian, D.; Ankem, M.; Cardelli, J.A. Tea polyphenols decrease serum levels of prostate-specific antigen, hepatocyte growth factor, and vascular endothelial growth factor in prostate cancer patients and inhibit production of hepatocyte growth factor and vascular endothelial growth factor in vitro. Cancer Prev. Res. (Phila.), 2009, 2(7), 673-682.
Nguyen, M.M.; Ahmann, F.R.; Nagle, R.B.; Hsu, C.H.; Tangrea, J.A.; Parnes, H.L.; Sokoloff, M.H.; Gretzer, M.B.; Chow, H.H. Randomized, double-blind, placebo-controlled trial of polyphenon E in prostate cancer patients before prostatectomy: Evaluation of potential chemopreventive activities. Cancer Prev. Res. (Phila.), 2012, 5(2), 290-298.
Zhu, M.; Chen, Y.; Li, R.C. Oral absorption and bioavailability of tea catechins. Planta Med., 2000, 66(5), 444-447.
Thomas, R.; Williams, M.; Sharma, H.; Chaudry, A.; Bellamy, P. A double-blind, placebo-controlled randomised trial evaluating the effect of a polyphenol-rich whole food supplement on PSA progression in men with prostate cancer--the U.K. NCRN Pomi-T study. Prostate Cancer Prostatic Dis., 2014, 17(2), 180-186.
Kumar, N.B.; Pow-Sang, J.; Egan, K.M.; Spiess, P.E.; Dickinson, S.; Salup, R.; Helal, M.; McLarty, J.; Williams, C.R.; Schreiber, F.; Parnes, H.L.; Sebti, S.; Kazi, A.; Kang, L.; Quinn, G.; Smith, T.; Yue, B.; Diaz, K.; Chornokur, G.; Crocker, T.; Schell, M.J. Randomized, placebo-controlled trial of green tea catechins for prostate cancer prevention. Cancer Prev. Res. (Phila.), 2015, 8(10), 879-887.
Guo, Y.; Zhi, F.; Chen, P.; Zhao, K.; Xiang, H.; Mao, Q.; Wang, X.; Zhang, X. Green tea and the risk of prostate cancer: A systematic review and meta-analysis. Medicine (Baltimore), 2017, 96(13)e6426
Fechtner, S.; Singh, A.; Chourasia, M.; Ahmed, S. Molecular insights into the differences in anti-inflammatory activities of green tea catechins on IL-1beta signaling in rheumatoid arthritis synovial fibroblasts. Toxicol. Appl. Pharmacol., 2017, 329, 112-120.
Sandhu, J.; Tu, H.Y.V. Recent advances in managing chronic prostatitis/chronic pelvic pain syndrome. F1000 Res., 2017, 6.
Yoon, B.I.; Ha, U.S.; Sohn, D.W.; Lee, S.J.; Kim, H.W.; Han, C.H.; Lee, C.B.; Cho, Y.H. Anti-inflammatory and antimicrobial effects of nanocatechin in a chronic bacterial prostatitis rat model. J. Infect. Chemother., 2011, 17(2), 189-194.
Naponelli, V.; Ramazzina, I.; Lenzi, C.; Bettuzzi, S.; Rizzi, F. Green tea catechins for prostate cancer prevention: Present achievements and future challenges. Antioxidants (Basel), 2017, 6(2)
Adhami, V.M.; Ahmad, N.; Mukhtar, H. Molecular targets for green tea in prostate cancer prevention. J. Nutr., 2003, 133(7)(Suppl.), 2417S-2424S.
Tsai, Y.J.; Chen, B.H. Preparation of catechin extracts and nanoemulsions from green tea leaf waste and their inhibition effect on prostate cancer cell PC-3. Int. J. Nanomedicine, 2016, 11, 1907-1926.
Malumbres, M. Cyclin-dependent kinases. Genome Biol., 2014, 15(6), 122.
Caporali, A.; Davalli, P.; Astancolle, S.; D’Arca, D.; Brausi, M.; Bettuzzi, S.; Corti, A. The chemopreventive action of catechins in the TRAMP mouse model of prostate carcinogenesis is accompanied by clusterin over-expression. Carcinogenesis, 2004, 25(11), 2217-2224.
Rizzi, F.; Bettuzzi, S. Clusterin (CLU) and prostate cancer. Adv. Cancer Res., 2009, 105, 1-19.
Giudice, A.; Montella, M.; Boccellino, M.; Crispo, A.; D’Arena, G.; Bimonte, S.; Facchini, G.; Ciliberto, G.; Botti, G.; Quagliuolo, L.; Caraglia, M.; Capunzo, M. Epigenetic changes induced by green tea catechins are associated with prostate cancer. Curr. Mol. Med., 2017, 17(6), 405-420.
Ngollo, M.; Dagdemir, A.; Karsli-Ceppioglu, S.; Judes, G.; Pajon, A.; Penault-Llorca, F.; Boiteux, J.P.; Bignon, Y.J.; Guy, L.; Bernard-Gallon, D.J. Epigenetic modifications in prostate cancer. Epigenomics, 2014, 6(4), 415-426.
Massie, C.E.; Mills, I.G.; Lynch, A.G. The importance of DNA methylation in prostate cancer development. J. Steroid Biochem. Mol. Biol., 2017, 166, 1-15.
Lall, R.K.; Syed, D.N.; Adhami, V.M.; Khan, M.I.; Mukhtar, H. Dietary polyphenols in prevention and treatment of prostate cancer. Int. J. Mol. Sci., 2015, 16(2), 3350-3376.
Ng, J.M.; Yu, J. Promoter hypermethylation of tumour suppressor genes as potential biomarkers in colorectal cancer. Int. J. Mol. Sci., 2015, 16(2), 2472-2496.
Khan, N.; Mukhtar, H. Modulation of signaling pathways in prostate cancer by green tea polyphenols. Biochem. Pharmacol., 2013, 85(5), 667-672.
Pandey, M.; Shukla, S.; Gupta, S. Promoter demethylation and chromatin remodeling by green tea polyphenols leads to re-expression of GSTP1 in human prostate cancer cells. Int. J. Cancer, 2010, 126(11), 2520-2533.
Kanwal, R.; Pandey, M.; Bhaskaran, N.; Maclennan, G.T.; Fu, P.; Ponsky, L.E.; Gupta, S. Protection against oxidative DNA damage and stress in human prostate by glutathione S-transferase P1. Mol. Carcinog., 2014, 53(1), 8-18.
Huang, J.; Tan, P.H.; Thiyagarajan, J.; Bay, B.H. Prognostic significance of glutathione S-transferase-pi in invasive breast cancer. Mod. Pathol., 2003, 16(6), 558-565.
Xiang, L.P.; Wang, A.; Ye, J.H.; Zheng, X.Q.; Polito, C.A.; Lu, J.L.; Li, Q.S.; Liang, Y.R. Suppressive effects of tea catechins on breast cancer. Nutrients, 2016, 8(8)
Yiannakopoulou, E.C. Targeting DNA methylation with green tea catechins. Pharmacology, 2015, 95(3-4), 111-116.
Rogovskii, V.S. The linkage between inflammation and immune tolerance: Interfering with inflammation in cancer. Curr. Cancer Drug Targets, 2017, 17(4), 325-332.
Garg, R.; Blando, J.M.; Perez, C.J.; Lal, P.; Feldman, M.D.; Smyth, E.M.; Ricciotti, E.; Grosser, T.; Benavides, F.; Kazanietz, M.G. COX-2 mediates pro-tumorigenic effects of PKCepsilon in prostate cancer. Oncogene, 2018, 37(34), 4735-4749.
Seeram, N.P.; Zhang, Y.; Nair, M.G. Inhibition of proliferation of human cancer cells and cyclooxygenase enzymes by anthocyanidins and catechins. Nutr. Cancer, 2003, 46(1), 101-106.
Ciccarelli, C.; Di Rocco, A.; Gravina, G.L.; Mauro, A.; Festuccia, C.; Del Fattore, A.; Berardinelli, P.; De Felice, F.; Musio, D.; Bouche, M.; Tombolini, V.; Zani, B.M.; Marampon, F. Disruption of MEK/ERK/c-Myc signaling radiosensitizes prostate cancer cells in vitro and in vivo. J. Cancer Res. Clin. Oncol., 2018, 144(9), 1685-1699.
Wang, M.; Lei, Y.X. Effects of tea polyphenols on proliferation and apoptosis of cadmium-transformed cells. Int. J. Clin. Exp. Med., 2015, 8(2), 3054-3062.
Yang, C.S.; Wang, H.; Chen, J.X.; Zhang, J. Effects of tea catechins on cancer signaling pathways. Enzymes, 2014, 36, 195-221.
Larsen, C.A.; Dashwood, R.H.; Bisson, W.H. Tea catechins as inhibitors of receptor tyrosine kinases: mechanistic insights and human relevance. Pharmacol. Res., 2010, 62(6), 457-464.
Li, M.; He, Z.; Ermakova, S.; Zheng, D.; Tang, F.; Cho, Y.Y.; Zhu, F.; Ma, W.Y.; Sham, Y.; Rogozin, E.A.; Bode, A.M.; Cao, Y.; Dong, Z. Direct inhibition of insulin-like growth factor-I receptor kinase activity by (-)-epigallocatechin-3-gallate regulates cell transformation. Cancer Epidemiol. Biomarkers Prev., 2007, 16(3), 598-605.
Tsao, R. Chemistry and biochemistry of dietary polyphenols. Nutrients, 2010, 2(12), 1231-1246.
Yang, H.; Landis-Piwowar, K.; Chan, T.H.; Dou, Q.P. Green tea polyphenols as proteasome inhibitors: implication in chemoprevention. Curr. Cancer Drug Targets, 2011, 11(3), 296-306.
Wang, X.; Song, K.S.; Guo, Q.X.; Tian, W.X. The galloyl moiety of green tea catechins is the critical structural feature to inhibit fatty-acid synthase. Biochem. Pharmacol., 2003, 66(10), 2039-2047.
Murase, T.; Misawa, K.; Haramizu, S.; Hase, T. Catechin-induced activation of the LKB1/AMP-activated protein kinase pathway. Biochem. Pharmacol., 2009, 78(1), 78-84.
Singh, B.N.; Shankar, S.; Srivastava, R.K. Green tea catechin, epigallocatechin-3-gallate (EGCG): Mechanisms, perspectives and clinical applications. Biochem. Pharmacol., 2011, 82(12), 1807-1821.
Le Bourvellec, C.; Renard, C.M. Interactions between polyphenols and macromolecules: Quantification methods and mechanisms. Crit. Rev. Food Sci. Nutr., 2012, 52(3), 213-248.
Pozdeev, A.O.; Rasadkina, E.N.; Burym, A.A.; Knyazev, V.V.; Koroteev, M.P.; Matyushin, A.I.; Koroteev, A.M.; Semeikin, A.V.; Shimanovskii, N.L. Synthesis and antiproliferative activity of new acylcatechins. Pharm. Chem. J., 2016, 50(8), 523-525.
Shirakami, Y.; Shimizu, M. Possible mechanisms of green tea and its constituents against cancer. Molecules, 2018, 23(9)
Oh, B.; Figtree, G.; Costa, D.; Eade, T.; Hruby, G.; Lim, S.; Elfiky, A.; Martine, N.; Rosenthal, D.; Clarke, S.; Back, M. Oxidative stress in prostate cancer patients: A systematic review of case control studies. Prostate Int., 2016, 4(3), 71-87.
Ellinger, S.; Muller, N.; Stehle, P.; Ulrich-Merzenich, G. Consumption of green tea or green tea products: is there an evidence for antioxidant effects from controlled interventional studies? Phytomedicine, 2011, 18(11), 903-915.
Lambert, J.D.; Elias, R.J. The antioxidant and pro-oxidant activities of green tea polyphenols: A role in cancer prevention. Arch. Biochem. Biophys., 2010, 501(1), 65-72.
Candeias, S.M.; Gaipl, U.S. The immune system in cancer prevention, development and therapy. Anticancer. Agents Med. Chem., 2016, 16(1), 101-107.
Janssen, L.M.E.; Ramsay, E.E.; Logsdon, C.D.; Overwijk, W.W. The immune system in cancer metastasis: Friend or foe? J. Immunother. Cancer, 2017, 5(1), 79.
Rogovskii, V.S. Mechanisms of immune tolerance in cancer and in normality. Russ. J. Immunol., 2015, 9(18), 171-185.
Graham, D.B.; Jasso, G.J.; Mok, A.; Goel, G.; Ng, A.C.Y.; Kolde, R.; Varma, M.; Doench, J.G.; Root, D.E.; Clish, C.B.; Carr, S.A.; Xavier, R.J. Nitric Oxide engages an anti-inflammatory feedback loop mediated by peroxiredoxin 5 in phagocytes. Cell Rep., 2018, 24(4), 838-850.
Rogovskii, V.S.; Shimanovskii, N.L.; Sergeeva, E.G. Immune mechanisms of and inflammatory reactions in cancer and their pharmacological regulation. Int. Med. J., 2016, 2, 77-86.
Morgillo, F.; Dallio, M.; Della Corte, C.M.; Gravina, A.G.; Viscardi, G.; Loguercio, C.; Ciardiello, F.; Federico, A. Carcinogenesis as a result of multiple inflammatory and oxidative hits: A comprehensive review from tumor microenvironment to gut microbiota. Neoplasia, 2018, 20(7), 721-733.
Kim, H.J.; Lee, S.Y.; Kim, D.S.; Kang, E.J.; Kim, J.S.; Choi, Y.J.; Oh, S.C.; Seo, J.H.; Kim, J.S. Inflammatory markers as prognostic indicators in pancreatic cancer patients who underwent gemcitabine- based palliative chemotherapy. Kor. J. Intern. Med, 2018.
Karan, D.; Dubey, S. From Inflammation to prostate cancer: The role of inflammasomes. Adv. Urol., 2016, 20163140372
Yli-Hemminki, T.H.; Laurila, M.; Auvinen, A.; Maattanen, L.; Huhtala, H.; Tammela, T.L.; Kujala, P.M. Histological inflammation and risk of subsequent prostate cancer among men with initially elevated serum Prostate-Specific Antigen (PSA) concentration in the Finnish prostate cancer screening trial. BJU Int., 2013, 112(6), 735-741.
Gurel, B.; Lucia, M.S.; Thompson, I.M., Jr; Goodman, P.J.; Tangen, C.M.; Kristal, A.R.; Parnes, H.L.; Hoque, A.; Lippman, S.M.; Sutcliffe, S.; Peskoe, S.B.; Drake, C.G.; Nelson, W.G.; De Marzo, A.M.; Platz, E.A. Chronic inflammation in benign prostate tissue is associated with high-grade prostate cancer in the placebo arm of the prostate cancer prevention trial. Cancer Epidemiol. Biomarkers Prev., 2014, 23(5), 847-856.
Min, K.J.; Kwon, T.K. Anticancer effects and molecular mechanisms of epigallocatechin-3-gallate. Integr. Med. Res., 2014, 3(1), 16-24.
Thomas, S.; Fisher, K.H.; Snowden, J.A.; Danson, S.J.; Brown, S.; Zeidler, M.P. Methotrexate is a JAK/STAT pathway inhibitor. PLoS One, 2015, 10(7)e0130078
Sponaas, A.M.; Yang, R.; Rustad, E.H.; Standal, T.; Thoresen, A.S.; Dao Vo, C.; Waage, A.; Slordahl, T.S.; Borset, M.; Sundan, A. PD1 is expressed on exhausted T cells as well as virus specific memory CD8+ T cells in the bone marrow of myeloma patients. Oncotarget, 2018, 9(62), 32024-32035.
Rawangkan, A.; Wongsirisin, P.; Namiki, K.; Iida, K.; Kobayashi, Y.; Shimizu, Y.; Fujiki, H.; Suganuma, M. Green Tea catechin is an alternative immune checkpoint inhibitor that inhibits pd-l1 expression and lung tumor growth. Molecules, 2018, 23(8)
Haffner, M.C.; Guner, G.; Taheri, D.; Netto, G.J.; Palsgrove, D.N.; Zheng, Q.; Guedes, L.B.; Kim, K.; Tsai, H.; Esopi, D.M.; Lotan, T.L.; Sharma, R.; Meeker, A.K.; Chinnaiyan, A.M.; Nelson, W.G.; Yegnasubramanian, S.; Luo, J.; Mehra, R.; Antonarakis, E.S.; Drake, C.G.; De Marzo, A.M. Comprehensive evaluation of programmed death-ligand 1 expression in primary and metastatic prostate cancer. Am. J. Pathol., 2018, 188(6), 1478-1485.
Calcinotto, A.; Spataro, C.; Zagato, E.; Di Mitri, D.; Gil, V.; Crespo, M.; De Bernardis, G.; Losa, M.; Mirenda, M.; Pasquini, E.; Rinaldi, A.; Sumanasuriya, S.; Lambros, M.B.; Neeb, A.; Luciano, R.; Bravi, C.A.; Nava-Rodrigues, D.; Dolling, D.; Prayer-Galetti, T.; Ferreira, A.; Briganti, A.; Esposito, A.; Barry, S.; Yuan, W.; Sharp, A.; de Bono, J.; Alimonti, A. IL-23 secreted by myeloid cells drives castration-resistant prostate cancer. Nature, 2018, 559(7714), 363-369.
Santilli, G.; Anderson, J.; Thrasher, A.J.; Sala, A. Catechins and antitumor immunity: Not MDSC’s cup of tea. OncoImmunology, 2013, 2(6)e24443
Kim, Y.H.; Won, Y.S.; Yang, X.; Kumazoe, M.; Yamashita, S.; Hara, A.; Takagaki, A.; Goto, K.; Nanjo, F.; Tachibana, H. Green tea catechin metabolites exert immunoregulatory effects on CD4(+) T Cell and natural killer cell activities. J. Agric. Food Chem., 2016, 64(18), 3591-3597.
Pasero, C.; Gravis, G.; Granjeaud, S.; Guerin, M.; Thomassin-Piana, J.; Rocchi, P.; Salem, N.; Walz, J.; Moretta, A.; Olive, D. Highly effective NK cells are associated with good prognosis in patients with metastatic prostate cancer. Oncotarget, 2015, 6(16), 14360-14373.
Babu, P.V.; Liu, D. Green tea catechins and cardiovascular health: An update. Curr. Med. Chem., 2008, 15(18), 1840-1850.
van het Hof, K.H.; Wiseman, S.A.; Yang, C.S.; Tijburg, L.B. Plasma and lipoprotein levels of tea catechins following repeated tea consumption. Proc. Soc. Exp. Biol. Med., 1999, 220(4), 203-209.
Mereles, D.; Hunstein, W. Epigallocatechin-3-gallate (EGCG) for clinical trials: More pitfalls than promises? Int. J. Mol. Sci., 2011, 12(9), 5592-5603.
Wang, P.; Aronson, W.J.; Huang, M.; Zhang, Y.; Lee, R.P.; Heber, D.; Henning, S.M. Green tea polyphenols and metabolites in prostatectomy tissue: Implications for cancer prevention. Cancer Prev. Res. (Phila.), 2010, 3(8), 985-993.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Page: [1223 - 1231]
Pages: 9
DOI: 10.2174/1871520619666190404153058
Price: $65

Article Metrics

PDF: 49