Nicotine Promotes Colon Tumor Growth and Angiogenesis through  -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.

Tobacco use and cancer survival: A cohort study of 40,230 Swedish male construction workers with incident cancer

“…In conclusion, use of tobacco, also the less harmful moist snuff (snus), 15 is associated with moderately increased cancer-specific mortality. Our data provide little guidance in regard to the mechanisms, which warrant further investigations, but our results concerning snus users seem to narrow in on nicotine as a conceivable culprit.…”

“…Although snus is harmful, 13 there is general consensus that its overall adverse health effects are only a fraction of those attributed to smoking. 14 Given that nicotine effects might influence tumor progression and possibly interfere with antitumor treatment, [5][6][7][15][16][17][18] our study aimed to investigate associations of tobacco use, divided into smoking and snus use, with cancer survival. Therefore, fatality according to self-reported tobacco use among new cases with any cancer was studied within a large cohort of male construction workers.…”

Sympathetic Neurotransmitters in Neuroblastoma – Between Physiology and Pathology

“…This effect is driven by -ARs present on cancer cells, the stimulation of which results in an increased release of angiogenic factors -vascular endothelial growth factor (VEGF) and interleukins 6 and 8 (IL-6 and IL-8) ( Fig. 3) (Nilsson et al, 2007;Thaker et al, 2006;Wong et al, 2007;Yang et al, 2009;Yang et al, 2006;Yang & Chou, 2004). Adrenergic stimulation has also been shown to increase the secretion of metalloproteases, MMP-2 and MMP-9, which further augments angiogenic and metastatic processes (Yang et al, 2006).…”

Exacerbation of Viral Myocarditis by Tobacco Smoke: The Catecholamine Hypothesis

“…A variety of sympathomimetic agents have been reported to induce or exacerbate myocarditis (Table 2). It is also important to note that nicotine has been shown to increase catecholamine levels in the blood (Wong et al, 2007). The most direct evidence arises from carefully controlled studies of murine myocarditis indicting that hypercatecholaminergeic states, secondary to pheochromocytoma and during infusion with sympathomimetic drugs, can cause or significantly exacerbate myocarditis (Cho et al, 1987;Van Vliet et al, 1966;Bindoli et al, 1992;Kammermeier & Grobecker, 1995;Davila et al, 1995;Prichard et al, 1991;Brown & O'Connell, 1995;Siltanen et al, l982;Haft, 1974;Noda, 1970;Morin & Cote, 1972;Seta et al, 1997;Nash & Carter, 1967;Karch, 1987;Krentz et al, 2001;Rezkalla et al, 1988).…”