Inhibitory mechanisms of tea polyphenols on the ultraviolet B-activated phosphatidylinositol 3-kinase-dependent pathway.

In this study, we investigated the effect of tea polyphenols, (-)-epigalloc atechin-3-gallate or theaflavins, on UVB-induced phosphatidylinositol 3-kin ase (PIM activation in mouse epidermal JB6 Cl 41 cells. Pretreatment of cel ls with these polyphenols inhibited UVB-induced PI3K activation. Furthermor e, UVB-induced activation of Akt and ribosomal p70 S6 kinase (p70 S6-K), PI 3K downstream effectors, were also attenuated by the polyphenols. In additi on to LY294002, a PI3K inhibitor, pretreatment with a specific mitogen-acti vated protein/ extracellular signal-regulated protein kinases (Erks) kinase I inhibitor, U0126, or a specific p38 kinase inhibitor, SB202190, blocked UVB-induced activation of both Akt and p70 S6-K. Pretreatment with LY294002 restrained UVB-induced phosphorylation of Erks, suggesting that in UVB sig naling, the Erk pathway is mediated by PI3K. Moreover, pretreatment with ra pamycin, an inhibitor of p70 S6-K, inhibited UVB-induced activation of p70 S6-K, but UVB-induced activation of Akt did not change. Interestingly, UVB- induced p70 S6-K activation was directly blocked by the addition of (-)-epi gallocatechin-3-gallate or theaflavins, whereas these polyphenols showed on ly a weak inhibition on UVB-induced Akt activation. Because PI3K is an impo rtant factor in carcinogenesis, the inhibitory effect of these polyphenols on activation of PI3K and its downstream effects may further explain the an ti-tumor promotion action of these tea constituents.