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[6]-Gingerol inhibits COX-2 expression by blocking the activation of p38 MAP kinase and NF-kBB in phorbol ester-stimulated mouse skin

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Authors
Kim, Sue Ok; Kundu, Joydeb Kumar; Shin, Young Kee; Park, Jin-Hong; Cho, Myung-Haing; Kim, Tae-Yoon; Surh, Young-Joon
Issue Date
2005
Publisher
Nature Publishing Group
Citation
Oncogene, 24, 2558–2567
Keywords
chemopreventioncyclooxygenase-2[6]-gingerolp38 MAPKNF-kBmouse skin
Abstract
[6]-Gingerol, a pungent ingredient of ginger (Zingiber officinale Roscoe, Zingiberaceae), has a wide array of pharmacologic effects. The present study was aimed at unraveling the molecular mechanisms underlying previously reported antitumor promoting effects of [6]-gingerol in mouse skin in vivo. One of the well-recognized molecular targets for chemoprevention is cyclooxygenase-2 (COX-2) that is abnormally upregulated in many premalignant and malignant tissues and cells. In our present study, topical application of [6]-gingerol inhibited COX-2 expression in mouse skin stimulated with a prototype tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Since the transcription factor nuclear factor-kappaB (NF-B) is known to regulate COX-2 induction, we attempted to determine the effect of [6]-gingerol on TPA-induced activation of NF-B. Pretreatment with [6]-gingerol resulted in a decrease in both TPA-induced DNA binding and transcriptional activities of NF-B through suppression of IB degradation and p65 nuclear translocation. Phosphorylation of both IB and p65 was substantially blocked by [6]-gingerol. In addition, [6]-gingerol inhibited TPA-stimulated interaction of phospho-p65-(Ser-536) with cAMP response element binding protein-binding protein, a transcriptional coactivator of NF-B. Moreover, [6]-gingerol prevented TPA-induced phosphorylation and catalytic activity of p38 mitogen-activated protein (MAP) kinase that regulates COX-2 expression in mouse skin. The p38 MAP kinase inhibitor SB203580 attenuated NF-B activation and subsequent COX-2 induction in TPA-treated mouse skin. Taken together, our data suggest that [6]-gingerol inhibits TPA-induced COX-2 expression in mouse skin in vivo by blocking the p38 MAP kinase-NF-B signaling pathway.
ISSN
0950-9232
Language
English
URI
http://hdl.handle.net/10371/73409
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College of Pharmacy (약학대학)Dept. of Pharmacy (약학과)Journal Papers (저널논문_약학과)
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