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

Cited 197 time in Web of Science Cited 235 time in Scopus
Authors
Kim, Sue Ok; Kundu, Joydeb Kumar; Shin, Young Kee; Park, Jin Hong; Cho, Myung-Haing; Kim, Tae-Yoon; Surh, Young-Joon
Issue Date
2005-04
Citation
Oncogene, Vol.24 No.15, pp.2558-2567
Keywords
chemopreventioncyclooxygenase-2[6]-gingerolp38 MAPKNF-kappa Bmouse 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-KB) is known to regulate COX-2 induction, we attempted to determine the effect of [6]- gingerol on TPA-induced activation of NF-KB. Pretreatment with [6]-gingerol resulted in a decrease in both TPA-induced DNA binding and transcriptional activities of NF-KB through suppression of IKB alpha degradation and p65 nuclear translocation. Phosphorylation of both IKB alpha 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-KB. 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-KB 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-KB signaling pathway.
ISSN
0950-9232
URI
https://hdl.handle.net/10371/172491
DOI
https://doi.org/10.1038/sj.onc.1208446
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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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