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Resveratrol modulates phorbol ester-induced pro-inflammatory signal transduction pathways in mouse skin in vivo: NF-κB and AP-1 as prime targets

Cited 142 time in Web of Science Cited 165 time in Scopus
Authors
Kundu, Joydeb Kumar; Shin, Young Kee; Surh, Young-Joon
Issue Date
2006-11
Publisher
PERGAMON-ELSEVIER SCIENCE LTD
Citation
Biochemical Pharmacology, Vol.72 No.11, pp.1506-1515
Keywords
resveratrolphorbol estercyclooxygenase-2transcription factorsI kappa B kinasemitogen-activated protein kinasemouse skin
Abstract
Functional abnormalities of intracellular signaling network cause the disruption in homeostasis maintained by critical cellular components, thereby accelerating premalignant and malignant transformation. Multiple lines of evidence suggest that an elevated expression of cyclooxygenase-2 (COX-2) is causally linked to tumorigenesis. The exposure to oxidative/pro-inflammatory stimuli turns on signaling arrays mediated by diverse classes of kinases and transcription factors, which may lead to aberrant expression of COX-2. We have attempted to unravel the signal transduction pathways involved in elevated COX-2 expression in mouse skin stimulated with a prototype tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) and its modulation by resveratrol, a phytoalexin known to exert potential chemopreventive effects. Our study revealed that topical application of TPA induced COX-2 expression in mouse skin via activation of nuclear factor-kappa B (NF-kappa B), which is regulated by upstream I kappa B kinase (IKK) or differentially by mitogen-activated protein (MAP) kinases. Besides NF-kappa B, the p38 MAP kinase-mediated activation of activator protein-1 (AP-1) has also been attributed to TPA-induced COX-2 expression in mouse skin. Among the MAP kinases, extracellular signal-regulated protein kinase (ERK) and p38 MAP kinase have been shown to regulate TPA-induced NF-kappa B activation, while p38 MAP kinase and c-Jun-N-terminal kinase are preferentially involved in TPA-induced activation of AP-1 in mouse skin in vivo. This commentary focuses on resveratrol modulation of intracellular signaling pathways involved in aberrant COX-2 expression in TPA-stimulated mouse skin to delineate molecular mechanisms underlying antitumor promoting effects of resveratrol. (c) 2006 Published by Elsevier Inc.
ISSN
0006-2952
Language
English
URI
https://hdl.handle.net/10371/80923
DOI
https://doi.org/10.1016/j.bcp.2006.08.005
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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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