Carcinogenesis, Vol 19, 551-556, Copyright © 1998 by Oxford University Press
WL Heusch and R Maneckjee
Although nicotine has been implicated as a potential factor in the
pathogenesis of human lung cancer, its mechanism of action in the
development of this cancer remains largely unknown. The present study
provides evidence that nicotine (a) activates the mitogen-activated protein
(MAP) kinase signalling pathway in lung cancer cells, specifically
extracellular signal-regulated kinase (ERK2), resulting in increased
expression of the bcl-2 protein and inhibition of apoptosis in these cells;
and (b) blocks the inhibition of protein kinase C (PKC) and ERK2 activity
in lung cancer cells by anti-cancer agents, such as therapeutic opioid
drugs, and thus can adversely affect cancer therapy. Nicotine appears to
have no effect on the activities of c-jun NH2- terminal protein kinase
(JNK) and p38 MAP kinases, which have also been shown to be involved in
apoptosis. While exposure to nicotine can result in the activation of the
two major signalling pathways (MAP kinase and PKC) that are known to
inhibit apoptosis, nicotine regulation of MAP (ERK2) kinase activity is not
dependent on PKC. These effects of nicotine occur at concentrations of 1
microM or less, that are generally found in the blood of smokers, and could
lead to disruption of the critical balance between cell death and
proliferation, resulting in the unregulated growth of cells. The findings
suggest caution in the use of smokeless tobacco products to treat smoking
addiction, as they could have a potentially deleterious effect in patients
with undetectable early tumour development.
ARTICLES
Signalling pathways involved in nicotine regulation of apoptosis of human lung cancer cells
Division of Surgical Oncology, Oregon Health Sciences University, Portland 97201-3098, USA.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  G. S. Maritz Are nicotine replacement therapy, varenicline or bupropion options for pregnant mothers to quit smoking? Effects on the respiratory system of the offspring Therapeutic Advances in Respiratory Disease, August 1, 2009; 3(4): 193 - 210. [Abstract] [PDF]
|
|
|
|
 |
|
 J. M. Huston, M. Rosas-Ballina, X. Xue, O. Dowling, K. Ochani, M. Ochani, M. M. Yeboah, P. K. Chatterjee, K. J. Tracey, and C. N. Metz Cholinergic Neural Signals to the Spleen Down-Regulate Leukocyte Trafficking via CD11b J. Immunol., July 1, 2009; 183(1): 552 - 559. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Wu, Z. Hu, D. Yu, L. Huang, G. Jin, J. Liang, H. Guo, W. Tan, M. Zhang, J. Qian, et al. Genetic Variants on Chromosome 15q25 Associated with Lung Cancer Risk in Chinese Populations Cancer Res., June 15, 2009; 69(12): 5065 - 5072. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Han, J. J. Gills, R. M. Memmott, S. Lam, and P. A. Dennis The Chemopreventive Agent Myoinositol Inhibits Akt and Extracellular Signal-Regulated Kinase in Bronchial Lesions from Heavy Smokers Cancer Prevention Research, April 1, 2009; 2(4): 370 - 376. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J R Ingram Nicotine: does it have a role in the treatment of skin disease? Postgrad. Med. J., April 1, 2009; 85(1002): 196 - 201. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Zhang, O. Kamdar, W. Le, G. D. Rosen, and D. Upadhyay Nicotine Induces Resistance to Chemotherapy by Modulating Mitochondrial Signaling in Lung Cancer Am. J. Respir. Cell Mol. Biol., February 1, 2009; 40(2): 135 - 146. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Guo, S. Ibaragi, T. Zhu, L.-Y. Luo, G.-F. Hu, P. S. Huppi, and C. Y. Chen Nicotine Promotes Mammary Tumor Migration via a Signaling Cascade Involving Protein Kinase C and cdc42 Cancer Res., October 15, 2008; 68(20): 8473 - 8481. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Song, H. S. Sekhon, X. W. Fu, M. Maier, Y. Jia, J. Duan, B. J. Proskosil, C. Gravett, J. Lindstrom, G. P. Mark, et al. Activated Cholinergic Signaling Provides a Target in Squamous Cell Lung Carcinoma Cancer Res., June 15, 2008; 68(12): 4693 - 4700. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Zheng, J. D. Ritzenthaler, J. Roman, and S. Han Nicotine Stimulates Human Lung Cancer Cell Growth by Inducing Fibronectin Expression Am. J. Respir. Cell Mol. Biol., December 1, 2007; 37(6): 681 - 690. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Zhang, X. Tang, Z.-F. Zhang, R. Velikina, S. Shi, and A. D. Le Nicotine Induces Hypoxia-Inducible Factor-1{alpha} Expression in Human Lung Cancer Cells via Nicotinic Acetylcholine Receptor Mediated Signaling Pathways Clin. Cancer Res., August 15, 2007; 13(16): 4686 - 4694. [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]
|
|
|
|
 |
|
 K. H. Ginzel, G. S. Maritz, D. F. Marks, M. Neuberger, Jim. R. Pauly, J. R. Polito, R. Schulte-Hermann, and T. A. Slotkin Critical Review: Nicotine for the Fetus, the Infant and the Adolescent? J Health Psychol, March 1, 2007; 12(2): 215 - 224. [Abstract] [PDF]
|
|
|
|
 |
|
 I. Madar, B. Bencherif, J. Lever, R. F. Heitmiller, S. C. Yang, M. Brock, J. Brahmer, H. Ravert, R. Dannals, and J. J. Frost Imaging {delta}- and {micro}-Opioid Receptors by PET in Lung Carcinoma Patients J. Nucl. Med., February 1, 2007; 48(2): 207 - 213. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Dasgupta, R. Kinkade, B. Joshi, C. DeCook, E. Haura, and S. Chellappan Nicotine inhibits apoptosis induced by chemotherapeutic drugs by up-regulating XIAP and survivin PNAS, April 18, 2006; 103(16): 6332 - 6337. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Bose, H. Zhang, K. B. Udupa, and P. Chowdhury Activation of p-ERK1/2 by nicotine in pancreatic tumor cell line AR42J: effects on proliferation and secretion Am J Physiol Gastrointest Liver Physiol, November 1, 2005; 289(5): G926 - G934. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Nakagawa, J. L. Oliva, D. Kothapalli, A. Fournier, R. K. Assoian, and M. G. Kazanietz Phorbol Ester-induced G1 Phase Arrest Selectively Mediated by Protein Kinase C{delta}-dependent Induction of p21 J. Biol. Chem., October 7, 2005; 280(40): 33926 - 33934. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. R. Gritz, C. Dresler, and L. Sarna Smoking, The Missing Drug Interaction in Clinical Trials: Ignoring the Obvious Cancer Epidemiol. Biomarkers Prev., October 1, 2005; 14(10): 2287 - 2293. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Guo, M. Chu, T. Abbeyquaye, and C.-Y. Chen Persistent Nicotine Treatment Potentiates Amplification of the Dihydrofolate Reductase Gene in Rat Lung Epithelial Cells as a Consequence of Ras Activation J. Biol. Chem., August 26, 2005; 280(34): 30422 - 30431. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Xin and X. Deng Nicotine Inactivation of the Proapoptotic Function of Bax through Phosphorylation J. Biol. Chem., March 18, 2005; 280(11): 10781 - 10789. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Chu, J. Guo, and C.-Y. Chen Long-term Exposure to Nicotine, via Ras Pathway, Induces Cyclin D1 to Stimulate G1 Cell Cycle Transition J. Biol. Chem., February 25, 2005; 280(8): 6369 - 6379. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Bao, X.-Y. He, X. Ding, S. Prabhu, and J.-Y. Hong METABOLISM OF NICOTINE AND COTININE BY HUMAN CYTOCHROME P450 2A13 Drug Metab. Dispos., February 1, 2005; 33(2): 258 - 261. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Arredondo, A. I. Chernyavsky, L. M. Marubio, A. L. Beaudet, D. L. Jolkovsky, K. E. Pinkerton, and S. A. Grando Receptor-Mediated Tobacco Toxicity: Regulation of Gene Expression through {alpha}3{beta}2 Nicotinic Receptor in Oral Epithelial Cells Am. J. Pathol., February 1, 2005; 166(2): 597 - 613. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Jin, F. Gao, T. Flagg, and X. Deng Nicotine Induces Multi-site Phosphorylation of Bad in Association with Suppression of Apoptosis J. Biol. Chem., May 28, 2004; 279(22): 23837 - 23844. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Campain Nicotine: Potentially a Multifunctional Carcinogen? Toxicol. Sci., May 1, 2004; 79(1): 1 - 3. [Full Text] [PDF]
|
|
|
|
|
|
S. Trombino, A. Cesario, S. Margaritora, P. Granone, G. Motta, C. Falugi, and P. Russo {alpha}7-Nicotinic Acetylcholine Receptors Affect Growth Regulation of Human Mesothelioma Cells: Role of Mitogen-Activated Protein Kinase Pathway Cancer Res., January 1, 2004; 64(1): 135 - 145. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. N. Ye, E. S. L. Liu, V. Y. Shin, W. K. K. Wu, J. C. Luo, and C. H. Cho Nicotine Promoted Colon Cancer Growth via Epidermal Growth Factor Receptor, c-Src, and 5-Lipoxygenase-Mediated Signal Pathway J. Pharmacol. Exp. Ther., January 1, 2004; 308(1): 66 - 72. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. B. Duncan, M. I. Schmidt, J. S. Pankow, C. M. Ballantyne, D. Couper, A. Vigo, R. Hoogeveen, A. R. Folsom, and G. Heiss Low-Grade Systemic Inflammation and the Development of Type 2 Diabetes: The Atherosclerosis Risk in Communities Study Diabetes, July 1, 2003; 52(7): 1799 - 1805. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Dunckley and R. J. Lukas Nicotine Modulates the Expression of a Diverse Set of Genes in the Neuronal SH-SY5Y Cell Line J. Biol. Chem., April 25, 2003; 278(18): 15633 - 15640. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Suzuki, E. Bayna, E. Dalle Molle, and W. Y. W. Lew Nicotine inhibits cardiac apoptosis induced by lipopolysaccharide in rats J. Am. Coll. Cardiol., February 5, 2003; 41(3): 482 - 488. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Aicher, C. Heeschen, M. Mohaupt, J. P. Cooke, A. M. Zeiher, and S. Dimmeler Nicotine Strongly Activates Dendritic Cell-Mediated Adaptive Immunity: Potential Role for Progression of Atherosclerotic Lesions Circulation, February 4, 2003; 107(4): 604 - 611. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Mai, W. S. May, F. Gao, Z. Jin, and X. Deng A Functional Role for Nicotine in Bcl2 Phosphorylation and Suppression of Apoptosis J. Biol. Chem., January 10, 2003; 278(3): 1886 - 1891. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. C. Briggs, H. I. Hall, E. A. Brann, C. J. Moriarty, and R. S. Levine Cigarette Smoking and Risk of Hodgkin's Disease: A Population-based Case-Control Study Am. J. Epidemiol., December 1, 2002; 156(11): 1011 - 1020. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. S. Conklin, W. Zhao, D.-S. Zhong, and C. Chen Nicotine and Cotinine Up-Regulate Vascular Endothelial Growth Factor Expression in Endothelial Cells Am. J. Pathol., February 1, 2002; 160(2): 413 - 418. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Hakki, K. Pennypacker, S. Eidizadeh, H. Friedman, and S. Pross Nicotine Inhibition of Apoptosis in Murine Immune Cells Experimental Biology and Medicine, November 1, 2001; 226(10): 947 - 953. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Gruslin, Q. Qiu, and B. K. Tsang Influence of Maternal Smoking on Trophoblast Apoptosis Throughout Development: Possible Involvement of Xiap Regulation Biol Reprod, October 1, 2001; 65(4): 1164 - 1169. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Hallquist, A. Hakki, L. Wecker, H. Friedman, and S. Pross Differential Effects of Nicotine and Aging on Splenocyte Proliferation and the Production of Th1- Versus Th2-Type Cytokines Experimental Biology and Medicine, July 1, 2000; 224(3): 141 - 146. [Abstract] [Full Text]
|
|
|
|
 |
|
 B.-H. Cao, K. Mortensen, D. Tornehave, and L.-I. Larsson Apoptosis in Rat Gastric Antrum: Evidence That Regulation by Food Intake Depends on Nitric Oxide Synthase J. Histochem. Cytochem., January 1, 2000; 48(1): 123 - 132. [Abstract] [Full Text]
|
|
|
|
|
|
A. Chen, B. H. Davis, M. Bissonnette, B. Scaglione-Sewell, and T. A. Brasitus 1,25-Dihydroxyvitamin D3 Stimulates Activator Protein-1-dependent Caco-2 Cell Differentiation J. Biol. Chem., December 10, 1999; 274(50): 35505 - 35513. [Abstract] [Full Text] [PDF]
|
|