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Resveratrol inhibits phorbol ester-induced cyclooxygenase-2 expression in mouse skin: MAPKs and AP-1 as potential molecular targets

Cited 62 time in Web of Science Cited 66 time in Scopus
Authors
Kundu, Joydeb Kumar; Chun, Kyung‐Soo; Kim, Sue O.; Surh, Young‐Joon
Issue Date
2004
Citation
BioFactors, Vol.21 No.1-4, pp.33-39
Keywords
chemopreventionresveratrolcyclooxygenase-2 (COX-2)activator protein-1mitogen-activated protein kinase (MAPK)mouse skin carcinogenesis
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.
ISSN
0951-6433
URI
https://hdl.handle.net/10371/172635
DOI
https://doi.org/10.1002/biof.552210108
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Graduate School of Convergence Science and Technology (융합과학기술대학원)Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과)Journal Papers (저널논문_분자의학 및 바이오제약학과)
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