title: Helional-induced activation of human olfactory receptor 2J3 promotes apoptosis and inhibits proliferation in a non-small-cell lung cancer cell line.
abstract: Studies within the last decade have localized the functional expression of olfactory receptors (ORs) to cells outside of the olfactory epithelium. In human hepatocarcinoma and prostate cancer cells, the activation of ORs by odors modulates elementary physiological processes and leads to an inhibitory effect on proliferation. Cells of the respiratory tract are in direct contact with the surrounding air, in which a myriad of volatile molecules, especially odors, are present. Non-small-cell lung cancer (NSCLC) has a high prevalence, a high mortality rate and is difficult to treat. NSCLC cells are nearly resistant to common chemotherapeutic approaches, and surgical resection provides the only possible chance of a cure for most patients. New approaches for the treatment of NSCLC are the focus of many current studies. Thus, it is of interest to characterize the functional expression of ORs in cancer cells of the lung and to investigate the impact of ORs on pathophysiological processes. In the present study, we demonstrate that the expression of OR2J3 and cytosolic Ca2+increase via the activation of the agonist helional in the NSCLC cell line A549. We further investigated the underlying pathway. Helional triggers phoshoinositol-3 kinase (PI3K), signaling the release of intracellular Ca2+and phosphorylation of ERK. We observed that OR2J3 activation induces apoptosis and inhibits cell proliferation and migration in long-term stimulus experiments with helional. Our study provides the first evidence of the functional expression of an OR in NSCLC cells and its putative therapeutic impact.
authors.affiliation: Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany. Electronic address: benjamin.kalbe@rub.de.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Kalbe
authors.affiliation: Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Viola Maria
authors.initials: VM
authors.lastname: Schulz
authors.affiliation: Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Marian
authors.initials: M
authors.lastname: Schlimm
authors.affiliation: Department of Pathology and Cytology, Augusta-Kranken-Anstalt, Bochum, Germany.
authors.forename: Stathis
authors.initials: S
authors.lastname: Philippou
authors.affiliation: Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Nikolina
authors.initials: N
authors.lastname: Jovancevic
authors.affiliation: Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Jansen
authors.affiliation: Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Paul
authors.initials: P
authors.lastname: Scholz
authors.affiliation: Department of Animal Physiology, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Lübbert
authors.affiliation: Department of Cell Morphology and Molecular Neurobiology, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Marvin
authors.initials: M
authors.lastname: Jarocki
authors.affiliation: Department of Cell Morphology and Molecular Neurobiology, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Faissner
authors.affiliation: Thoraxzentrum Ruhrgebiet, Department of Thoracic Surgery, Evangelisches Krankenhaus Herne, Herne, Germany.
authors.forename: Erich
authors.initials: E
authors.lastname: Hecker
authors.affiliation: Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Sophie
authors.initials: S
authors.lastname: Veitinger
authors.affiliation: Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Teresa
authors.initials: T
authors.lastname: Tsai
authors.affiliation: Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Osterloh
authors.affiliation: Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Hanns
authors.initials: H
authors.lastname: Hatt
mesh_terms: D017209:Apoptosis; D020013:Calcium Signaling; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D009363:Neoplasm Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D018035:Receptors, Odorant / Q000819:agonists / Q000235:genetics / Q000378:metabolism*
chemical_list: D009363:Neoplasm Proteins; D018035:Receptors, Odorant
keywords: Apoptosis; Cell physiology; GPCR; NSCLC; Olfactory receptor; Signaling