Inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced NF-kappaB activation by tea polyphenols, (-)-epigallocatechin gallate and theaflavins.
(-)-Epigallocatechin gallate (EGCG) and theaflavins are believed to be the key active components in tea for the chemoprevention of cancer. However, the molecular mechanisms by which EGCG and theaflavins block carcinogenesis are not clear. In the JB6 mouse epidermal cell line a tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), which causes cell transformation at high frequency, markedly induced NF-kappaB activation. We found that EGCG and theaflavins inhibited TPA-induced NF-kappaB activity in a concentration-dependent manner. These polyphenols blocked TPA-induced phosphorylation of IkappaBalpha at Ser32 in the same concentration range. Moreover, the NF-kappaB sequence-specific DNA-binding activity induced by TPA was also inhibited by these polyphenols. These results suggest that inhibition of NF-kappaB activation is also important in accounting for the anti-tumor promotion effects of EGCG and theaflavins.
Nomura
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The Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, MN 55912, USA.
Ma
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Chen
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Bode
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AM
Dong
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D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D044946:Biflavonoids; D002273:Carcinogens / Q000037:antagonists & inhibitors* / Q000633:toxicity; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D004817:Epidermis / Q000187:drug effects; D005419:Flavonoids; D020672:I-kappa B Proteins / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D010636:Phenols / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011108:Polymers / Q000494:pharmacology; D013662:Tea / Q000737:chemistry; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors* / Q000633:toxicity; D015533:Transcriptional Activation / Q000187:drug effects
D016588:Anticarcinogenic Agents; D044946:Biflavonoids; D002273:Carcinogens; D005419:Flavonoids; D020672:I-kappa B Proteins; D016328:NF-kappa B; D010636:Phenols; D011108:Polymers; D013662:Tea; C056068:theaflavin; D002392:Catechin; D004247:DNA; C045651:epigallocatechin gallate; D013755:Tetradecanoylphorbol Acetate