title: Paroxetine-induced Ca2+ movement and death in OC2 human oral cancer cells.
abstract: The effect of the antidepressant paroxetine on cytosolic free Ca2+ concentrations ([Ca2+]i) in OC2 human oral cancer cells is unclear. This study explored whether paroxetine changed basal [Ca2+]i levels in suspended OC2 cells by using fura-2 as a Ca2+-sensitive fluorescent dye. Paroxetine at concentrations between 100-1,000 microM increased [Ca2+]i in a concentration-dependent manner. The Ca2+ signal was reduced by 50% by removing extracellular Ca2+. Paroxetine-induced Ca2+ influx was inhibited by the store-operated Ca2+ channel blockers nifedipine, econazole and SK&F96365, and protein kinase C modulators. In Ca2+-free medium, pretreatment with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin abolished paroxetine-induced [Ca2+]i rise. Inhibition of phospholipase C with U73122 did not alter paroxetine-induced [Ca2+]i rise. Paroxetine at 10-50 microM induced cell death in a concentration-dependent manner. The death was not reversed when cytosolic Ca2+ was chelated with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid. Propidium iodide staining suggests that apoptosis plays a role in the death. Collectively, in OC2 cells, paroxetine induced [Ca2+]i rise by causing phospholipase C-independent Ca2+ release from the endoplasmic reticulum and Ca2+ influx via store-operated Ca2+ channels in a manner regulated by protein kinase C and phospholipase A2. Paroxetine (up to 50 microM) induced cell death in a Ca2+-independent manner.
authors.affiliation: Laboratory Medicine Division, Zuoying Armed Forces General Hospital, Kaohsiung 813, Taiwan, ROC.
authors.forename: Yi-Chien
authors.initials: YC
authors.lastname: Fang
authors.forename: Chiang-Ting
authors.initials: CT
authors.lastname: Chou
authors.forename: Chih-Chuan
authors.initials: CC
authors.lastname: Pan
authors.forename: Yao-Dung
authors.initials: YD
authors.lastname: Hsieh
authors.forename: Wei-Zhe
authors.initials: WZ
authors.lastname: Liang
authors.forename: David
authors.initials: D
authors.lastname: Chao
authors.forename: Jeng-Yu
authors.initials: JY
authors.lastname: Tsai
authors.forename: Wei-Chuan
authors.initials: WC
authors.lastname: Liao
authors.forename: Daih-Huang
authors.initials: DH
authors.lastname: Kuo
authors.forename: Pochuen
authors.initials: P
authors.lastname: Shieh
authors.forename: Chun-Chi
authors.initials: CC
authors.lastname: Kuo
authors.forename: Chung-Ren
authors.initials: CR
authors.lastname: Jan
authors.forename: Chen-Fu
authors.initials: CF
authors.lastname: Shaw
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism*; D045744:Cell Line, Tumor; D004963:Estrenes / Q000494:pharmacology; D006801:Humans; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D017374:Paroxetine / Q000494:pharmacology*; D054467:Phospholipases A2 / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology; D011760:Pyrrolidinones / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
chemical_list: D002118:Calcium; D004963:Estrenes; D017374:Paroxetine; D054467:Phospholipases A2; D011493:Protein Kinase C; D011760:Pyrrolidinones; D017367:Selective Serotonin Reuptake Inhibitors; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione