title: Nicotine-induced cellular stresses and autophagy in human cancer colon cells: A supportive effect on cell homeostasis via up-regulation of Cox-2 and PGE(2) production.
abstract: Nicotine, one of the active components in cigarette smoke, has been described to contribute to the protective effect of smoking in ulcerative colitis (UC) patients. Furthermore, the nicotinic acetylcholine receptor α7 subunit (α7nAChR) expressed on immune cells, is an essential regulator of inflammation. As intestinal epithelial cells also express α7nAChR, we investigated how nicotine could participate in the homeostasis of intestinal epithelial cells. First, using the human adenocarcinoma cell line HT-29, we revealed that nicotine, which triggers an influx of extracellular Ca(2+) following α7nAChR stimulation, induces mitochondrial reactive oxygen species (ROS) production associated with a disruption of the mitochondrial membrane potential and endoplasmic reticulum stress. This results in caspase-3 activation, which in turn induces apoptosis. Additionally, we have shown that nicotine induces a PI3-K dependent up-regulation of cyclooxygenase-2 (Cox-2) expression and prostaglandin E2 (PGE2) production. In this context, we suggest that this key mediator participates in the cytoprotective effects of nicotine against apoptosis by stimulating autophagy in colon cancer cells. Our results provide new insight into one potential mechanism by which nicotine could protect from UC and suggest an anti-inflammatory role for the cholinergic pathway at the epithelial cell level.
authors.affiliation: INSERM U836, Equipe du Stress et des Interactions Neurodigestives, BP 170, Grenoble Cedex 09, F-38042, France; Université Joseph Fourier, Grenoble Institut des Neurosciences, BP170 Grenoble Cedex 09, F-38041, France.
authors.forename: Marjolaine A
authors.initials: MA
authors.lastname: Pelissier-Rota
authors.affiliation: CNRS UMR 5163, Equipe Génomique et Evolution des Microorganismes, BP170 Grenoble Cedex 9, F-38042, France; Université Joseph Fourier, Laboratoire Adaptation et Pathogénie des Microorganismes, BP170 Grenoble Cedex 09, F-38041, France.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Pelosi
authors.affiliation: Université Joseph Fourier, Centre Universitaire de Biologie Expérimentale, BP 53, Grenoble Cedex 09, F-38041, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Meresse
authors.affiliation: INSERM U836, Equipe du Stress et des Interactions Neurodigestives, BP 170, Grenoble Cedex 09, F-38042, France; Université Joseph Fourier, Grenoble Institut des Neurosciences, BP170 Grenoble Cedex 09, F-38041, France. Electronic address: muriel.jacquier-sarlin@ujf-grenoble.fr.
authors.forename: Muriel R
authors.initials: MR
authors.lastname: Jacquier-Sarlin
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015232:Dinoprostone / Q000096:biosynthesis* / Q000378:metabolism; D019073:HT29 Cells; D006706:Homeostasis; D006801:Humans; D009538:Nicotine / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D017382:Reactive Oxygen Species; D009538:Nicotine; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D015232:Dinoprostone
keywords: Autophagy; Cell homeostasis; Colorectal cancer; Cox-2; Nicotine; PGE(2)