QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.104.068031v1 311/1/123    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ye, Y. N. Articles by Cho, C. H. Search for Related Content PubMed PubMed Citation Articles by Ye, Y. N. Articles by Cho, C. H.

GASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

The Modulating Role of Nuclear Factor-B in the Action of 7-Nicotinic Acetylcholine Receptor and Cross-Talk between 5-Lipoxygenase and Cyclooxygenase-2 in Colon Cancer Growth Induced by 4-(N-Methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone

Department of Pharmacology, Faculty of Medicine, Zhejiang University, China (Y.N.Y.); and Department of Pharmacology, Faculty of Medicine, The University of Hong Kong, China (Y.N.Y., E.S.L.L., V.Y.S., W.K.K.W., C.H.C.)

4-(N-Methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), the tobacco-specific nitrosamine, induces lung cancer in all animal species tested and is thought to contribute significantly to the high lung cancer burden associated with smoking. However, there is no report whether NNK could promote colon cancer growth. To address this hypothesis and the possible signaling pathways involved, we used SW1116 colon cancer cell line to study these biological events in vitro. Results showed that NNK, after 5-h treatment, stimulated cell proliferation, enhanced 7-nicotinic acetylcholine receptor (7-nAChR) mRNA levels and nuclear factor-B (NF-B) DNA binding activity, as well as 5-lipoxygenase and cyclooxygenase-2 protein expressions. -Bungarotoxin, the specific 7-nAChR antagonist, inhibited these biological effects. However, 5-lipoxygenase inhibition had no effect on 7-nAChR mRNA expression, but significantly inhibited cell proliferation and activation of NF-B and cyclooxygenase-2, whereas NF-B-specific inhibitor caffeic acid phenethyl ester reduced both cell proliferation and cyclooxygenase expression induced by NNK without affecting 7-nAChR mRNA level and 5-lipoxygenase expression. Together, the present study demonstrated that NNK promoted colon cancer growth in vitro. NF-B not only conveys the biological effect of 7-nAChR activation but is also involved in the cross-talk between 5-lipoxygenase and cyclooxygenase-2 in response to NNK in colon cancer cell development.

Address correspondence to: Prof. C. H. Cho, Department of Pharmacology, Faculty of Medicine, The University of Hong Kong, 1/F Li Shu Fan Bldg., 5 Sassoon Rd., Hong Kong, China. E-mail: chcho{at}hkusua.hku.hk

This article has been cited by other articles:

				S. W. Chung, A. Toriba, H. Y. Chung, B. P. Yu, T. Kameda, N. Tang, R. Kizu, and K. Hayakawa Activation of 5-Lipoxygenase and NF-{kappa}B in the Action of Acenaphthenequinone by Modulation of Oxidative Stress Toxicol. Sci., January 1, 2008; 101(1): 152 - 158. [Abstract] [Full Text] [PDF]

				H. P. S. Wong, L. Yu, E. K. Y. Lam, E. K. K. Tai, W. K. K. Wu, and C.-H. Cho Nicotine Promotes Colon Tumor Growth and Angiogenesis through {beta}-Adrenergic Activation Toxicol. Sci., June 1, 2007; 97(2): 279 - 287. [Abstract] [Full Text] [PDF]

				E. A. Jaimes, R.-X. Tian, and L. Raij Nicotine: the link between cigarette smoking and the progression of renal injury? Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H76 - H82. [Abstract] [Full Text] [PDF]

				J. Arredondo, A. I. Chernyavsky, D. L. Jolkovsky, K. E. Pinkerton, and S. A. Grando Receptor-mediated tobacco toxicity: cooperation of the Ras/Raf-1/MEK1/ERK and JAK-2/STAT-3 pathways downstream of {alpha}7 nicotinic receptor in oral keratinocytes FASEB J, October 1, 2006; 20(12): 2093 - 2101. [Abstract] [Full Text] [PDF]

				W. K.K. Wu, H. P.S. Wong, S. W. Luo, K. Chan, F. Y. Huang, M. K.C. Hui, E. K.Y. Lam, V. Y. Shin, Y. N. Ye, Y. H. Yang, et al. 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone from Cigarette Smoke Stimulates Colon Cancer Growth via {beta}-Adrenoceptors Cancer Res., June 15, 2005; 65(12): 5272 - 5277. [Abstract] [Full Text] [PDF]

				F. R. Hirsch and S. M. Lippman Advances in the Biology of Lung Cancer Chemoprevention J. Clin. Oncol., May 10, 2005; 23(14): 3186 - 3197. [Abstract] [Full Text] [PDF]