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.