Effect of the antidepressant paroxetine on Ca 2+ movement in PC3 human prostate cancer cells

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