Phenethyl isothiocyanate induces Ca2+ movement and cytotoxicity in PC3 human prostate cancer cells

The effect of phenethyl isothiocyanate (PEITC), a cruciferous vegetable-derived compound, on cytoplasmic free Ca2+ concentrations ([Ca2+]i) in prostate cells has not been explored. This study examined whether PEITC altered [Ca2+]i levels in suspended human prostate PC3 cancer cells loaded with the Ca2+-sensitive dye fura-2. PEITC caused [Ca2+]i rises in a concentration-dependent manner with an EC50 of 192 μM. Removing extracellular Ca2+ reduced the Ca2+ signal by 42%. PEITC-induced [Ca2+]i rise in Ca2+-containing medium was not affected by modulation of protein kinase C activity, but was inhibited by 90% by the phospholipase A2 inhibitor aristolochic acid (20 μM). In Ca2+-free medium, the PEITC-induced [Ca2+]i rise was changed by depleting store Ca2+ with 1 μM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor). Conversely, PEITC pretreatment abolished thapsigargin-induced [Ca2+]i rise. Chelation of cytosolic Ca2+ with BAPTA did not reverse the decreased cell viability. Collectively, the data suggest that in PC3 cells, PEITC induced a [Ca2+]i increase by causing Ca2+ release from endoplasmic reticulum in a phospholipase A2-dependent fashion and by inducing Ca2+ influx. PEITC decreased cell viability in a concentration-dependent, Ca2+-independent manner. Moreover, the effect of allyl isothiocyanate (AITC), benzyl isothiocyanate (BITC) and PEITC on Ca2+ signaling has also been compared.