Effect of the antidepressant maprotiline on Ca2+ movement and proliferation in human prostate cancer cells

1. The effect of maprotiline, an antidepressant, on human prostate cells is unclear. In the present study, the effect of maprotiline on [Ca 2 + ] i and growth in PC3 human prostate cancer cells was measured using the fluorescent dyes fura-2 and tetrazolium, respectively. 2. Maprotiline caused a rapid, concentration-dependent increase in [Ca 2 + ] i (EC 5 0 = 200 μmol/L). The maprotiline-induced [Ca 2 + ] i increase was reduced by removal of extracellular Ca 2 + or pretreatment with nicardipine. 3. The maprotiline-induced Mn 2 + influx-associated fura-2 fluorescence quench directly suggests that maprotiline caused Ca 2 + influx. 4. In Ca 2 + -free medium, thapsigargin, an inhibitor of the endoplasmic reticulum Ca 2 + -ATPase, caused a monophasic [Ca 2 + ] i increase, after which the effects of maprotiline of increasing [Ca 2 + ] i were abolished. In addition, pretreatment with maprotiline reduced a major portion of the thapsigargin-induced increase in [Ca 2 + ] i . 5. U73122, an inhibitor of phospholipase C, abolished the ATP (but not maprotiline)-induced increase in [Ca 2 + ] i . 6. Overnight incubation with 1-10 μmol/L maprotiline did not alter cell proliferation, although incubation with 30-50 μmol/L maprotiline decreased cell proliferation. 7, These findings suggest that maprotiline rapidly increases [Ca 2 + ] i in human prostate cancer cells by stimulating both extracellular Ca 2 + influx and intracellular Ca 2 + release and that it may modulate cell proliferation in a concentration-dependent manner.