Inhibition of ultraviolet B-induced c-fos gene expression and p38 mitogen-activated protein kinase activation by (-)-epigallocatechin gallate in a human keratinocyte cell line

(-)-Epigallocatechin gallate (EGCG), the major polyphenol isolated from green tea, is an active chemoprevention agent against cancer. However, the molecular mechanisms that underlie the inhibitory effects of EGCG are not well understood. In this study, we tested the effects of EGCG on ultraviolet (UV) B radiation-induced c-fos gene expression in a human keratinocyte cell line, HaCaT. EGCG inhibited UVB-induced steady-state message and transcriptional activation of the c-fos gene in a dose-dependent manner. Western analyses further indicated that EGCG had an inhibitory effect on UVB- induced accumulation of the c-fos protein within the same dose range. To further examine the mechanism by which EGCG inhibits UVB-induced c-fos expression, we tested the effect of EGCG on upstream activators of the c-fos gene. We found that EGCG significantly inhibited activation of p38 mitogen- activated protein kinase but not c-jun NH₂-terminal kinase or extracellular signal-regulated protein kinase activation. Our previous studies have indicated that UVB-induced c-fos expression may play a key role in UVB- induced activation of the activator protein-1 transcription factor and EGCG- inhibited, UVB-induced activation of AP-1 in HaCaT cells. Because AP-1 is important for tumor promotion and c-fos is a major component of AP-1, the inhibitory effects of EGCG on c-fos expression may further explain the anti- tumor-promoting effects of EGCG.