Carcinogenesis Advance Access originally published online on November 21, 2003
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Carcinogenesis, Vol. 25, No. 3, 445-454,
March 2004
Carcinogenesis vol.25 no.3 © Oxford University Press 2004; all rights reserved.
CARCINOGENESIS |
Nitric oxide induces expression of cyclooxygenase-2 in mouse skin through activation of NF-
B
College of Pharmacy, Seoul National University, Shinlim-dong, Kwanak-ku, Seoul 151742, South Korea and 1 College of Dentistry, Yonsei University, Seoul 120-749, South Korea
Inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) are frequently overexpressed in tumor tissues or transformed cells. In the present work, we assessed the effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) on expression of iNOS and COX-2 in mouse skin. Topical application to the dorsal skin of female ICR mice of 10 nmol TPA led to maximal induction of iNOS and COX-2 protein expression at 
2 and 4 h, respectively. When applied topically onto shaven backs of mice 30 min prior to TPA, the NOS inhibitor aminoguanidine (AG) inhibited the expression of COX-2 protein at the pharmacologically effective dose. Pretreatment with a more specific iNOS inhibitor, NG-nitro-L-arginine-methyl ester, also suppressed TPA-induced COX-2 expression. Immunohistochemical analysis of TPA-treated mouse skin using an anti-nitrotyrosine antibody reveals enhanced levels of nitrotyrosine protein localized in epidermal and dermal layers. Topical application of NO donors, such as sodium nitroprusside (SNP) and S-nitroso-N-acetyl-D,L-penicillamine, induced expression of COX-2 in mouse skin, which was attenuated by the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl imidazoline-1-oxyl 3-oxide. SNP treatment stimulated NF-
B activation in mouse skin, which was associated with the degradation of IB
. Topical application of inhibitors of NF-B, such as pyrrolidine dithiocarbamate or N--p-tosyl-L-lysine chloromethylketone, inhibited the SNP-induced COX-2 expression. SNP induced a weak but concentration-related increase in COX-2 expression in cultured mouse keratinocytes, which was abolished by treatment with SN50, a specific inhibitor of nuclear translocation of NF-B. Mouse keratinocytes treated with SNP exhibited an elevated NF-B-driven COX-2 promoter activity. Topical application of AG (10 µmol) prior to each TPA treatment after initiation reduced the multiplicity of papillomas by 44% at 22 weeks. In conclusion, up-regulation of COX-2 by NO may be mediated by activation of NF-B in mouse skin, which provides a molecular mechanism by which COX-2 is induced during tumor promotion.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. R. Radke, Z. K. Siddiqui, T. A. Miura, J. M. Routes, and J. L. Cook E1A Oncogene Enhancement of Caspase-2-Mediated Mitochondrial Injury Sensitizes Cells to Macrophage Nitric Oxide-Induced Apoptosis J. Immunol., June 15, 2008; 180(12): 8272 - 8279. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Zhou, V. N. Ivanov, Y.-C. Lien, M. Davidson, and T. K. Hei Mitochondrial Function and Nuclear Factor-{kappa}B-Mediated Signaling in Radiation-Induced Bystander Effects Cancer Res., April 1, 2008; 68(7): 2233 - 2240. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-S. Lai, S. Li, C.-Y. Chai, C.-Y. Lo, C.-T. Ho, Y.-J. Wang, and M.-H. Pan Inhibitory effect of citrus 5-hydroxy-3,6,7,8,3',4'-hexamethoxyflavone on 12-O-tetradecanoylphorbol 13-acetate-induced skin inflammation and tumor promotion in mice Carcinogenesis, December 1, 2007; 28(12): 2581 - 2588. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Ying, A. B. Hofseth, D. D. Browning, M. Nagarkatti, P. S. Nagarkatti, and L. J. Hofseth Nitric Oxide Inactivates the Retinoblastoma Pathway in Chronic Inflammation Cancer Res., October 1, 2007; 67(19): 9286 - 9293. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Y. Chung, J. H. Park, M. J. Kim, H. O. Kim, J. K. Hwang, S. K. Lee, and K. K. Park Xanthorrhizol inhibits 12-O-tetradecanoylphorbol-13-acetate-induced acute inflammation and two-stage mouse skin carcinogenesis by blocking the expression of ornithine decarboxylase, cyclooxygenase-2 and inducible nitric oxide synthase through mitogen-activated protein kinases and/or the nuclear factor-{kappa}B Carcinogenesis, June 1, 2007; 28(6): 1224 - 1231. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Karpuzoglu, J. B. Fenaux, R. A. Phillips, A. J. Lengi, F. Elvinger, and S. Ansar Ahmed Estrogen Up-Regulates Inducible Nitric Oxide Synthase, Nitric Oxide, and Cyclooxygenase-2 in Splenocytes Activated with T Cell Stimulants: Role of Interferon-{gamma} Endocrinology, February 1, 2006; 147(2): 662 - 671. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-J. Surh, J. K. Kundu, H.-K. Na, and J.-S. Lee Redox-Sensitive Transcription Factors as Prime Targets for Chemoprevention with Anti-Inflammatory and Antioxidative Phytochemicals J. Nutr., December 1, 2005; 135(12): 2993S - 3001S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Birnbaum, Y. Ye, S. Rosanio, S. Tavackoli, Z.-Y. Hu, E. R. Schwarz, and B. F. Uretsky Prostaglandins mediate the cardioprotective effects of atorvastatin against ischemia-reperfusion injury Cardiovasc Res, February 1, 2005; 65(2): 345 - 355. [Abstract] [Full Text] [PDF]
|
|