Resveratrol inhibits phorbol ester-induced cyclooxygenase-2 expression in mouse skin: MAPKs and AP-1 as potential molecular targets
Article first published online: 16 DEC 2008
Copyright © 2004 International Union of Biochemistry and Molecular Biology, Inc.
Volume 21, Issue 1-4, pages 33–39, 2004
How to Cite
Kundu, J. K., Chun, K.-S., Kim, S. O. and Surh, Y.-J. (2004), Resveratrol inhibits phorbol ester-induced cyclooxygenase-2 expression in mouse skin: MAPKs and AP-1 as potential molecular targets. BioFactors, 21: 33–39. doi: 10.1002/biof.552210108
- Issue published online: 16 DEC 2008
- Article first published online: 16 DEC 2008
- Biogreen Project, Republic of Korea
- Seoul National University
- cyclooxygenase-2 (COX-2);
- activator protein-1;
- mitogen-activated protein kinase (MAPK);
- mouse skin carcinogenesis
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.