Effect of the Antidepressant Paroxetine on Ca2+ Movement in PC3 Human Prostate Cancer Cells

The effect of the antidepressant paroxetine on cytosolic free Ca2+ concentrations ([Ca2+](i)) in PC3 human prostate cancer cells is unclear. This study explored whether paroxetine changed basal [Ca2+](i) levels in suspended PC3 cells by using fura-2 as a Ca2+-sensitive fluorescent dye. Paroxetine at concentrations between 10-150 mu M increased [Ca2+](i) in a concentration-dependent manner. The Ca2+ signal was reduced by 55% by removing extracellular Ca2+. Paroxetine-induced Ca2+ influx was inhibited by the store-operated Ca2+ channel blockers econazole and SK&F96365, the phospholipase A2 inhibitor aristolochic acid, and protein kinase C modulators. In Ca2+-free medium, pretreatment with the endoplasmic reticulum Ca2+ pump inhibitors thapsigargin, 2,5-di-tert-butylhydroquinone (BHQ), or cyclopiazonic acid (CPA) all abolished paroxetine-induced [Ca2+](i) rise. Inhibition of phospholipase C with U73122 inhibited paroxetine-induced [Ca2+](i) rise by 80%. Collectively, in PC3 cells, paroxetine induced [Ca2+](i) rise by causing phospholipase C-dependent 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. Drug Dev Res, 71:120-126, 2010. (C) 2009 Wiley-Liss, Inc.