Affiliations: College of Pharmacy, Seoul National University, Seoul
151-742, South Korea
Note: [] Address for correspondence: Professor Young-Joon Surh, College
of Pharmacy, Seoul National University, Shinlim-dong, Kwanak-ku, Seoul 151-742,
South Korea. Tel.: + 82 2 880 7845; Fax: + 82 2 874 9775; E-mail:
[email protected]
Abstract: 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.
