title: Nicotine-mediated cell proliferation and angiogenesis: new twists to an old story.
abstract: Tobacco smoking is one of the major etiologic factors associated with cancer. While there are many carcinogenic compounds present in tobacco smoke, its main addictive component, nicotine, is not carcinogenic by itself. The addictive properties of nicotine are achieved through the nicotinic acetylcholine receptors (nAChRs) that are widely distributed in the brain and neuromuscular junctions; at the same time, they were found to be expressed in a variety of non-neuronal tissues in the body including those of the lung. Recent studies show that these non-neuronal nAChRs can induce cell proliferation and angiogenesis. Analysis of the molecular mechanisms underlying nicotine-mediated cell proliferation showed the involvement of Src kinase and the scaffolding protein beta-arrestin-1. Further, nAChRs were found to activate the basic components of the cell cycle machinery similar to growth factor receptors. This involved increased binding of Raf-1 kinase to the Rb protein, activation of cyclins D and E as well as induction of proliferative promoters. This article describes pathway involved in nicotine-induced cell proliferation and angiogenesis and the potential steps that are amenable for developing novel anti-cancer therapies.
authors.affiliation: Drug Discovery Program, Department of Interdisciplinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, Florida 33612, USA.
authors.forename: Piyali
authors.initials: P
authors.lastname: Dasgupta
authors.forename: Srikumar P
authors.initials: SP
authors.lastname: Chellappan
mesh_terms: D002453:Cell Cycle; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000139:chemically induced*; D009538:Nicotine / Q000009:adverse effects*; D011978:Receptors, Nicotinic / Q000502:physiology
chemical_list: D011978:Receptors, Nicotinic; D009538:Nicotine