Effect of the antidepressant paroxetine on Ca²⁺ movement in PC3 human prostate cancer cells

(Table Presented) 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 μM 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 Ca ²⁺ release from the endoplasmic reticulum and Ca²⁺ influx via store-operated Ca²⁺ channels in a manner regulated by protein kinase C and phospholipase A2.