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Resveratrol inhibits phorbol ester‐induced cyclooxygenase‐2 expression in mouse skin: MAPKs and AP‐1 as potential molecular targets
Author(s) -
Kundu Joydeb Kumar,
Chun KyungSoo,
Kim Sue O.,
Surh YoungJoon
Publication year - 2004
Publication title -
biofactors
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.204
H-Index - 94
eISSN - 1872-8081
pISSN - 0951-6433
DOI - 10.1002/biof.552210108
Subject(s) - resveratrol , mapk/erk pathway , kinase , p38 mitogen activated protein kinases , activator (genetics) , chemistry , protein kinase a , carcinogenesis , signal transduction , phosphorylation , 12 o tetradecanoylphorbol 13 acetate , biochemistry , protein kinase c , microbiology and biotechnology , pharmacology , biology , phorbol ester , receptor , gene
Multiple lines of evidence from laboratory studies suggest that resveratrol, a polyphenolic antioxidant present in grapes, has potent chemopreventive activity. Resveratrol has been reported to inhibit chemically‐induced carcinogenesis in mouse skin, but the underlying mechanisms remain unclarified. Since an abnormally elevated level of cyclooxygenase‐2 (COX‐2) has been implicated in carcinogenesis, we investigated the effect of resveratrol on 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA)‐induced COX‐2 expression in mouse skin. Pretreatment of dorsal skin of female ICR mice with resveratrol inhibited TPA‐induced COX‐2 expression in a dose dependent manner. To elucidate the molecular mechanism underlying COX‐2 inhibition by resveratrol, we examined its effect on TPA‐induced activation of mitogen‐activated protein kinases (MAPK) and transcription factors which regulate COX‐2 expression. Resveratrol pretreatment resulted in a decrease in the phosphorylation of extracellular signal‐regulated protein kinase (ERK) as well as the catalytic activity of ERK and p38 MAPK. In addition, resveratrol prevented TPA‐induced DNA binding of activator protein‐1 (AP‐1). Taken together, suppression of COX‐2 expression by blocking the activation of MAPKs and AP‐1 may represent possible molecular mechanisms responsible for previously reported anti‐tumor promoting effects of resveratrol on mouse skin carcinogenesis.