Carcinogenesis Advance Access originally published online on February 12, 2006
Carcinogenesis 2006 27(7):1465-1474; doi:10.1093/carcin/bgi349
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Resveratrol inhibits phorbol ester-induced expression of COX-2 and activation of NF-
B in mouse skin by blocking IB kinase activity
National Research Laboratory of Molecular Carcinogenesis and Chemoprevention, College of Pharmacy, Seoul National University, Seoul 151-742 and 1 Graduate School of East-West Medical Science, Kyunghee University, Yongin 449-701, Korea
* To whom correspondence should be addressed at: College of Pharmacy, Seoul National University, Shillim-dong, Kwanak-ku, Seoul 151-742, Korea. Tel: +82 2 880 7845; Fax: +82 2 874 9775; Email: surh{at}plaza.snu.ac.kr
Aberrant expression of cyclooxygenase-2 (COX-2) has been implicated in tumor promotion. Resveratrol, a phytoalexin present in grapes, was reported to inhibit multistage mouse skin carcinogenesis. In the present study, we found that topically applied resveratrol significantly inhibited COX-2 expression induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Resveratrol-suppressed phosphorylation and subsequent degradation of I
B
, thereby inhibiting activation of nuclear factor-B (NF-B) in TPA-stimulated mouse skin. Pretreatment with resveratrol also suppressed TPA-induced phosphorylation of extracellular signal-regulated protein kinase (ERK) and p38 mitogen-activated protein (MAP) kinase. Resveratrol blunted TPA-induced phosphorylation of p65 and its interaction with CBP/p300, rendering NF-B transcriptionally inactive. To get further insights into the molecular basis of NF-B inactivation by resveratrol, we examined the role of IB kinase (IKK) in mediating TPA-induced activation of NF-B and COX-2 expression. TPA treatment led to rapid induction of IKK activity in mouse skin, which was abolished either by resveratrol or an IKK inhibitor Bay 11-7082. Topical application of Bay 11-7082 also abrogated TPA-induced NF-B activation and COX-2 expression, supporting the involvement of IKK in TPA-induced COX-2 expression. Taken together, the above findings suggest that resveratrol targets IKK in blocking TPA-induced NF-B activation and COX-2 expression in mouse skin in vivo.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. S. PARK, K. M. KIM, M. H. KIM, H. J. CHANG, M. K. BAEK, S. M. KIM, and Y. D. JUNG Resveratrol Inhibits Tumor Cell Adhesion to Endothelial Cells by Blocking ICAM-1 Expression Anticancer Res, January 1, 2009; 29(1): 355 - 362. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Singh, R. Chaturvedi, M. Asim, D. P. Barry, N. D. Lewis, M. P. Vitek, and K. T. Wilson The Apolipoprotein E-mimetic Peptide COG112 Inhibits the Inflammatory Response to Citrobacter rodentium in Colonic Epithelial Cells by Preventing NF-{kappa}B Activation J. Biol. Chem., June 13, 2008; 283(24): 16752 - 16761. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-C. Lu, H.-C. Lai, S.-C. Hsieh, and J.-K. Chen Resveratrol ameliorates Serratia marcescens-induced acute pneumonia in rats J. Leukoc. Biol., April 1, 2008; 83(4): 1028 - 1037. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-Y. Lin, H.-Y. Tang, T. Keating, Y.-H. Wu, A. Shih, D. Hammond, M. Sun, A. Hercbergs, F. B. Davis, and P. J. Davis Resveratrol is pro-apoptotic and thyroid hormone is anti-apoptotic in glioma cells: both actions are integrin and ERK mediated Carcinogenesis, January 1, 2008; 29(1): 62 - 69. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. E. Harper, B. B. Patel, J. Wang, A. Arabshahi, I. A. Eltoum, and C. A. Lamartiniere Resveratrol suppresses prostate cancer progression in transgenic mice Carcinogenesis, September 1, 2007; 28(9): 1946 - 1953. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-L. Su, C.-Y. Yang, M. Zhao, M.-L. Kuo, and M.-L. Yen Forkhead Proteins Are Critical for Bone Morphogenetic Protein-2 Regulation and Anti-tumor Activity of Resveratrol J. Biol. Chem., July 6, 2007; 282(27): 19385 - 19398. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-C. Lee, J. K. Kundu, D.-M. Hwang, H.-K. Na, and Y.-J. Surh Humulone inhibits phorbol ester-induced COX-2 expression in mouse skin by blocking activation of NF-{kappa}B and AP-1: I{kappa}B kinase and c-Jun-N-terminal kinase as respective potential upstream targets Carcinogenesis, July 1, 2007; 28(7): 1491 - 1498. [Abstract] [Full Text] [PDF]
|
|