title: Nicotine promotes colon tumor growth and angiogenesis through beta-adrenergic activation.
abstract: Cigarette smoking is a putative environmental risk factor for colon cancer. Nicotine, an active alkaloid in tobacco, has been implicated in carcinogenesis. In the present study, we demonstrated that oral nicotine administration (50 or 200 microg/ml) for 25 days stimulated growth of human colon cancer xenograft in nude mice. It also increased vascularization in the tumors and elevated cotinine and adrenaline plasma levels. beta-Adrenoceptors, cyclooxygenase-2 (COX-2), prostaglandin E(2) (PGE(2)), and vascular endothelial growth factor (VEGF) in tumor tissues were also increased by nicotine. I.p. injection of beta(1)-selective antagonist (atenolol, 5 or 10 mg/kg) or beta(2)-selective antagonist (ICI 118,551, 5, or 10 mg/kg) blocked the nicotine-stimulated tumor growth dose dependently, in which beta(2)-selective antagonist produced a more prominent effect. beta-Adrenoceptors blockade also abrogated the stimulatory action of nicotine on microvessel densities as well as cell expression of COX-2, PGE(2), and VEGF, in which beta(2)-selective antagonist produced a significant effect. These findings provide a direct evidence that nicotine can enhance colon tumor growth mediated partly by stimulation of beta-adrenoceptors, preferentially the beta(2)-adrenoceptors. Activation of beta-adrenoceptors and the subsequent stimulation of COX-2, PGE(2), and VEGF expression is perhaps an important mechanism in the tumorigenic action of nicotine on colon tumor growth. These data suggest that beta-adrenoceptors play a modulatory role in the development of colon cancer and partly elucidate the carcinogenic action of cigarette smoke.
authors: Department of Pharmacology, The University of Hong Kong, Hong Kong, China.
authors: Helen Pui Shan
authors: HP
authors: Wong
authors: Le
authors: L
authors: Yu
authors: Emily Kai Yee
authors: EK
authors: Lam
authors: Emily Kin Ki
authors: EK
authors: Tai
authors: William Ka Kei
authors: WK
authors: Wu
authors: Chi-Hin
authors: CH
authors: Cho
mesh_terms: D000318:Adrenergic beta-Agonists; D000818:Animals; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology*; D003367:Cotinine / Q000097:blood; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004837:Epinephrine / Q000097:blood; D019073:HT29 Cells; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000139:chemically induced* / Q000473:pathology*; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects* / Q000235:genetics; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000318:Adrenergic beta-Agonists; D018722:Nicotinic Agonists; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D042461:Vascular Endothelial Growth Factor A; D009538:Nicotine; D051546:Cyclooxygenase 2; D003367:Cotinine; D015232:Dinoprostone; D004837:Epinephrine