title: 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.
authors.affiliation: Department of Biology, University of Northern Iowa, Cedar Falls, IA 50614, USA. lisa.beltz@uni.edu
authors.forename: Lisa Ann
authors.initials: LA
authors.lastname: Beltz
authors.forename: Diana Kay
authors.initials: DK
authors.lastname: Bayer
authors.forename: Amber Lynn
authors.initials: AL
authors.lastname: Moss
authors.forename: Ira Mitchell
authors.initials: IM
authors.lastname: Simet
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D016718:Arachidonic Acid / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology / Q000627:therapeutic use*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009362:Neoplasm Metastasis / Q000503:physiopathology; D009369:Neoplasms / Q000503:physiopathology / Q000517:prevention & control*; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D009569:Nitric Oxide / Q000378:metabolism; D009857:Oncogenes / Q000187:drug effects; D010084:Oxidation-Reduction / Q000187:drug effects; D010636:Phenols / Q000494:pharmacology / Q000627:therapeutic use*; D059808:Polyphenols; D061988:Proteasome Inhibitors; D017382:Reactive Oxygen Species / Q000378:metabolism; D011944:Receptors, Androgen / Q000187:drug effects; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects; D017978:Receptors, Growth Factor / Q000096:biosynthesis / Q000187:drug effects; D013662:Tea; D016615:Telomere / Q000187:drug effects; D013762:Tetrahydrofolate Dehydrogenase / Q000187:drug effects; D019014:fas Receptor / Q000378:metabolism
chemical_list: D000975:Antioxidants; D005419:Flavonoids; D008077:Lipoproteins, LDL; D016328:NF-kappa B; D010636:Phenols; D059808:Polyphenols; D061988:Proteasome Inhibitors; D017382:Reactive Oxygen Species; D011944:Receptors, Androgen; D018336:Receptors, Aryl Hydrocarbon; D017978:Receptors, Growth Factor; D013662:Tea; D019014:fas Receptor; D016718:Arachidonic Acid; D009569:Nitric Oxide; D002392:Catechin; C045651:epigallocatechin gallate; D013762:Tetrahydrofolate Dehydrogenase