Nicotine-induced cellular stresses and autophagy in human cancer colon cells: A supportive effect on cell homeostasis via up-regulation of Cox-2 and PGE2 production |
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| Institution: | 1. Université catholique de Louvain, Secteur des Sciences de la Santé, Institut de Recherche Expérimentale et Clinique, Pôle de Chirurgie Expérimentale et Transplantation (CHEX), Avenue Mounier 55, B-1200 Brussels, Belgium;2. Cardiac Surgery Department, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland;3. Cliniques universitaires Saint-Luc, Service d''orthopédie et de traumatologie de l''appareil locomoteur, Avenue Hippocrate 10, B-1200 Brussels, Belgium;4. Cliniques universitaires Saint-Luc, Service d''anatomopathologie, Avenue Hippocrate 10, B-1200 Brussels, Belgium |
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| 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 Ca2+ 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. |
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| Keywords: | Nicotine Colorectal cancer Autophagy Cox-2 Cell homeostasis nAChR"} {"#name":"keyword" "$":{"id":"kw0040"} "$$":[{"#name":"text" "_":"nicotinic acetylcholine receptor IBD"} {"#name":"keyword" "$":{"id":"kw0050"} "$$":[{"#name":"text" "_":"inflammatory bowel disease Cox-2"} {"#name":"keyword" "$":{"id":"kw0060"} "$$":[{"#name":"text" "_":"Cyclooxygenase 2 prostaglandin E2 UC"} {"#name":"keyword" "$":{"id":"kw0080"} "$$":[{"#name":"text" "_":"ulcerative colitis ROS"} {"#name":"keyword" "$":{"id":"kw0090"} "$$":[{"#name":"text" "_":"reactive oxygen species PI3-K"} {"#name":"keyword" "$":{"id":"kw0100"} "$$":[{"#name":"text" "_":"phosphatidylinositol-3-kinase |
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