1. Mechanisms of cancer prevention by green and black tea polyphenols.
- Author
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Beltz LA, Bayer DK, Moss AL, and Simet IM
- Subjects
- Animals, Antioxidants pharmacology, Apoptosis drug effects, Arachidonic Acid metabolism, Catechin metabolism, Catechin therapeutic use, Cell Cycle drug effects, Cell Proliferation drug effects, Flavonoids pharmacology, Gene Expression drug effects, Humans, Lipid Peroxidation drug effects, Lipoproteins, LDL metabolism, NF-kappa B metabolism, Neoplasm Metastasis physiopathology, Neoplasms physiopathology, Neovascularization, Pathologic prevention & control, Nitric Oxide metabolism, Oncogenes drug effects, Oxidation-Reduction drug effects, Phenols pharmacology, Polyphenols, Proteasome Inhibitors, Reactive Oxygen Species metabolism, Receptors, Androgen drug effects, Receptors, Aryl Hydrocarbon drug effects, Receptors, Growth Factor biosynthesis, Receptors, Growth Factor drug effects, Telomere drug effects, Tetrahydrofolate Dehydrogenase drug effects, fas Receptor metabolism, Catechin analogs & derivatives, Flavonoids therapeutic use, Neoplasms prevention & control, Phenols therapeutic use, Tea
- 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.
- Published
- 2006
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