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Tobacco components activate the acetylcholine signaling pathway in bronchioalveolar carcinoma
Author(s) -
Lau Jamie K.,
Brown Kathleen C.,
Crabtree Clayton M.,
Dom Aaron M.,
Buckley Adam W.,
Harman Jarrod C.,
Dasgupta Piyali
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.479.1
Subject(s) - acetylcholine , acetylcholine receptor , vesicular acetylcholine transporter , nicotine , nicotinic agonist , chemistry , nicotinic acetylcholine receptor , cholinergic , pharmacology , signal transduction , hedgehog signaling pathway , a549 cell , receptor , microbiology and biotechnology , biochemistry , apoptosis , biology , choline acetyltransferase , endocrinology , neuroscience
Nicotine, the addictive component of cigarettes, accelerates cell proliferation and angiogenesis through nicotinic acetylcholine receptors (nAChRs). We show for the first time that acetylcholine (ACh) stimulates proliferation of A549 and H358 human bronchioalveolar carcinoma (BAC) cells. The maximal proliferation of human BACs was observed at 2 μmol. Furthermore, we observed that nicotine induced the production of ACh in a concentration and time‐dependent manner. The pro‐secretory activity of nicotine was mediated via α7‐ and β3‐containing‐nAChRs. Western blotting and ELISA analysis indicates that proteins involved in ACh signaling pathway, vesicular acetylcholine transporter (VAChT), choline transporter 1 (CHT1) and acetylecholinesterase (AChE), are expressed on A549 and H358 human BACs. Finally, VAChT and CHT1 inhibitors (vesamicol and hemicholium respectively) caused robust apoptosis of A549 and H358 cells and had little effect on normal lung cells. Our observations raise the possibility that tobacco components like nicotine promote the growth of human BACs by stimulating ACh production. Further, the disruption of this process may have applications in BAC therapy.