title: Nicotine inhibition of apoptosis suggests a role in tumor promotion.
abstract: Recent evidence indicates that cell death through apoptosis may be an important mechanism to prevent tumor development. Therefore, agents that inhibit apoptosis may function as tumor promoters. The purpose of this study was to determine the effects of nicotine on the process of apoptosis. The results demonstrate that nicotine inhibits apoptosis induced by diverse stimuli including tumor necrosis factor (TNF), UV light, chemotherapeutic drugs, and calcium ionophore. This phenomenon was observed in normal and transformed cells derived from a variety of species and tissues, including tumor cell types related to tobacco use. The major nicotine metabolite, cotinine, also inhibited apoptosis, whereas N-nitrosodiethylamine, a carcinogen found in tobacco, was without effect. Therefore, nicotine-mediated inhibition of apoptosis may contribute to the pathogenesis of tobacco-related cancer as well as decrease the efficacy of cancer therapies.
authors.affiliation: Palo Alto Institute of Molecular Medicine, Mountain View, CA 94043.
authors.forename: S C
authors.initials: SC
authors.lastname: Wright
authors.forename: J
authors.initials: J
authors.lastname: Zhong
authors.forename: H
authors.initials: H
authors.lastname: Zheng
authors.forename: J W
authors.initials: JW
authors.lastname: Larrick
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000139:chemically induced*; D009538:Nicotine / Q000633:toxicity*; D013237:Stereoisomerism; D013601:T-Lymphocytes / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014466:Ultraviolet Rays
chemical_list: D000970:Antineoplastic Agents; D014409:Tumor Necrosis Factor-alpha; D009538:Nicotine