Inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced NF-kappa B 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, th e molecular mechanisms by which EGCG and theaflavins block carcinogenesis a re not clear. In the JB6 mouse epidermal cell line a tumor promoter 12-O-te tradecanoylphorbol-13-acetate (TPA), which causes cell transformation at hi gh frequency, markedly induced NF-kappaB activation. We found that EGCG and theaflavins inhibited TPA-induced NF-kappaB activity in a concentration-de pendent manner. These polyphenols blocked TPA-induced phosphorylation of I kappaB alpha at Ser32 in the same concentration range. Moreover, the NF-kap paB sequence-specific DNA-binding activity induced by TPA was also inhibite d by these polyphenols. These results suggest that inhibition of NF-kappaB activation is also important in accounting for the anti-tumor promotion eff ects of EGCG and theaflavins.