Inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced NF-κB 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-κB activation. We found that EGCG and theaflavins inhibited TPA-induced NF-κB activity in a concentration-dependent manner. These polyphenols blocked TPA-induced phosphorylation of IκBα at Ser32 in the same concentration range. Moreover, the NF-κB sequence-specific DNA-binding activity induced by TPA was also inhibited by these polyphenols. These results suggest that inhibition of NF-κB activation is also important in accounting for the anti-tumor promotion effects of EGCG and theaflavins.