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
Wx. Chen et al., 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, MOL CARCINO, 24(2), 1999, pp. 79-84
(-)-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.