Paroxetine-Induced Ca2+ Movement and Death in OC2 Human Oral Cancer Cells

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 mu M 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 mu M 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 mu M) induced cell death in a Ca2+-independent manner.