Multiple roles of nicotine on cell proliferation and inhibition of apoptosis: implications on lung carcinogenesis.
The genotoxic effects of tobacco carcinogens have long been recognized, the contribution of tobacco components to cancerogenesis by cell surface receptor signaling is relatively unexplored. Nicotine, the principal tobacco alkaloid, acts through nicotinic acetylcholine receptor (nAChR). nAChR are functionally present on human lung airway epithelial cells, on lung carcinoma [SCLC and NSCLC] and on mesothelioma and build a part of an autocrine-proliferative network that facilitates the growth of neoplastic cells. Different nAChR subunit gene expression patterns are expressed between NSCLC from smokers and non-smokers. Although there is no evidence that nicotine itself could induce cancer, different studies established that nicotine promotes in vivo the growth of cancer cells and the proliferation of endothelial cells suggesting that nicotine might contribute to the progression of tumors already initiated. These observations led to the hypothesis that nicotine might be playing a direct role in the promotion and progression of human lung cancers. Here, we briefly overview the role and the effects of nicotine on pulmonary cell growth and physiology and its feasible implications in lung carcinogenesis.
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Cancer Unit, National Cancer Research Institute, Genoa, Italy.
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Paleari
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D017209:Apoptosis / Q000187:drug effects*; D002273:Carcinogens / Q000633:toxicity; D049109:Cell Proliferation / Q000187:drug effects*; D004847:Epithelial Cells / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects*; D008175:Lung Neoplasms / Q000209:etiology*; D008654:Mesothelioma / Q000473:pathology; D008958:Models, Molecular; D009389:Neovascularization, Pathologic / Q000139:chemically induced; D009538:Nicotine / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity*; D011978:Receptors, Nicotinic / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects; D012907:Smoking / Q000009:adverse effects; D014407:Tumor Cells, Cultured
D002273:Carcinogens; D011978:Receptors, Nicotinic; D009538:Nicotine