Effect of m-3M3FBS on Ca2+ movement in PC3 human prostate cancer cells

The effect of 2,4,6-trimethyl-N-(meta-3-trifluoromethyl-phenyl)-benzenesulfonamide (m-3M3FBS), a presumed phospholipase C activator, on cytosolic free Ca2+ concentrations (Ca2+]i) in PC3 human prostate cancer cells is unclear. This study explored whether m-3M3FBS changed basal Ca2+]i levels in suspended PC3 cells by using fura-2 as a Ca2+-sensitive fluorescent dye. M-3M3FBS at concentrations between 10-50 microM increased Ca2+]i in a concentration-dependent manner. The Ca2+ signal was reduced by 60% by removing extracellular Ca2+. M-3M3FBS-induced Ca2+ influx was inhibited by the store-operated Ca2+ channel blockers nifedipine, econazole and SK&F96365, and by the phospholipase A2 inhibitor aristolochic acid. In Ca2+-free medium, 30 microM m-3M3FBS pretreatment greatly inhibited the Ca2+]i rise induced by the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin or BHQ. Conversely, pretreatment with thapsigargin, BHQ or cyclopiazonic acid reduced the major part of m-3M3FBS-induced Ca2+]i rise. Inhibition of phospholipase C with U73122 did not much alter m-3M3FBS-induced Ca2+]i rise. Collectively, in PC3 cells, m-3M3FBS induced Ca2+]i rises by causing phospholipase C-independent Ca2+ release from the endoplasmic reticulum and Ca2+ influx via store-operated Ca2+ channels.