Mechanisms of Cancer Prevention by Green and Black Tea Polyphenols

Abstract

Drinking green tea is associated with decreased frequency of cancer development. This review outlines the wide range of mechanisms by which epigallocatechin gallate (ECGC) and other green and black tea polyphenols inhibit cancer cell survival. EGCG suppressed androgen receptor expression and signalling via several growth factor receptors. Cell cycle arrest or apoptosis involved caspase activation and altered Bcl-2 family member expression. EGCG inhibited telomerase activity and led to telomere fragmentation. While at high concentrations polyphenols had pro-oxidative activities, at much lower levels, anti-oxidative effects occurred. Nitric oxide production was reduced by EGCG and black tea theaflavins by suppressing inducible nitric oxide synthase via blocking nuclear translocation of the transcription factor nuclear factor-kappaB as a result of decreased IkappaB kinase activity. Polyphenols up- or down-regulated activity of a number of key enzymes, including mitogen-activated protein kinases and protein kinase C, and increased or decreased protein/mRNA levels, including that of cyclins, oncogenes, and tumor suppressor genes. Metastasis was inhibited via effects on urokinase and matrix metalloproteinases. Polyphenols reduced angiogenesis, in part by decreasing vascular endothelial growth factor production and receptor phosphorylation. Recent work demonstrated that EGCG reduced dihydrofolate reductase activity, which would affect nucleic acid and protein synthesis. It also acted as an aryl hydrocarbon receptor an-tagonist by directly binding the receptor's molecular chaperone, heat shock protein 90. In conclusion, green and black tea polyphenols act at numerous points regulating cancer cell growth, survival, and metastasis, including effects at the DNA, RNA, and protein levels.

Green Tea for Endometriosis

“…The potent effects of tea polyphenols toward inflammation have also been known to cancer prevention (Beltz et al, 2006). Tea polyphenols appear to modulate at different targets the anti-inflammatory activities related to arachidonic acid-dependent pathways, such as cyclooxygenase (COX) inhibition.…”

“…They act as a pleiotropic substance, which influencing multiple mechanisms that are involved in carcinogenesis (Beltz et al, 2006;Khan et al, 2006) through suppressing angiogenesis (Kondo et al, 2002;Zhu et al, 2007). With these basic finding, recent direction pointed out that the anti-angiogenic and anti-oxidation properties of ECGC may be a promising therapeutic agent in treating endometriosis.…”

The Past and Future of Studies on Tea and Cancer Prevention

“…The possible cancer-preventive activity by tea drinking has received much attention in the past three decades (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). Accumulating evidence on the anti-cancer activity of tea drinking has focused mainly on the tea catechins, especially EGCG, because the chemically deˆned EGCG and EGCG-enriched fractions such as Polyphenon E (PolyE) were provided by a tea manufacturer.…”

“…Anticarcinogenic eŠects of tea polyphenols have been reported in the tissues/organs of skin, esophagus, stomach, colon, bladder, lung, liver, pancreas, prostate, and mammary glands in various animal models (8,11,12). Polyphenols play potential roles in many mechanisms, including reduction of oxidative stress, modiˆcation of carcinogen metabolism, prevention/repair of DNA damage, cell cycle arrest, suppression of tumor promotion, apoptotic death in pre-cancerous/cancerous cells, inhibition of metastasis, and modulation of oncogenic signal transduction (6,8). EGCG has recently been reported to bind to speciˆc targets, i.e., the 67-kDa laminin receptor, vimentin and Fyn, which may alter the downstream signal transduction beneˆting suppression of tumor formation (6,13).…”

“…Polyphenols play potential roles in many mechanisms, including reduction of oxidative stress, modiˆcation of carcinogen metabolism, prevention/repair of DNA damage, cell cycle arrest, suppression of tumor promotion, apoptotic death in pre-cancerous/cancerous cells, inhibition of metastasis, and modulation of oncogenic signal transduction (6,8). EGCG has recently been reported to bind to speciˆc targets, i.e., the 67-kDa laminin receptor, vimentin and Fyn, which may alter the downstream signal transduction beneˆting suppression of tumor formation (6,13). Indeed, much evidence on the cancer preventive eŠects of tea polyphenols has been reported in in vitro and animal experiments, but there is insu‹cient and inconsistent evidence on the associations between tea consumption and cancer incidence and mortality (7).…”