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 (ECCC), the major polyphenol isolated from gre en tea, is an active chemoprevention agent against cancer. However, the mol ecular mechanisms that underlie the inhibitory effects of EGCG are not well understood. In this study, we tested the effects of EGCG on ultraviolet (U V) B radiation-induced c-fos gene expression in a human keratinocyte cell l ine, HaCaT. EGCG inhibited UVB-induced steady-state message and transcripti onal activation of the c-fos gene in a dose-dependent manner. Western analy ses further indicated that EGCG had an inhibitory effect on UVB-induced acc umulation of the c-fos protein within the same dose range. To further exami ne the mechanism by which EGCG inhibits UVB-induced c-fos expression, we te sted the effect of EGCG on upstream activators of the c-fos gene. We found that ECCC significantly inhibited activation of p38 mitogen-activated prote in kinase but not c-jun NH2-terminal kinase or extracellular signal-regulat ed protein kinase activation. Our previous studies have indicated that UVB- induced c-fos expression may play a key role in UVB-induced activation of t he activator protein-1 transcription factor and EGCG-inhibited, UVB-induced activation of AP-1 in HaCaT cells. Because AP-1 is important for tumor pro motion and c-fos is a major component of AP-1, the inhibitory effects of EG CG on c-fos expression may further explain the anti-tumor-promoting effects of EGCG. Mol. Carcinog. 24:79-84, 1999. (C) 1999 Wiley-Liss, Inc.