Effect of diallyl disulfide on Ca2+ movement and viability in PC3 human prostate cancer cells

The effect of diallyl disulfide (DADS) on cytosolic Ca2+ concentrations ([Ca2+](i)) and viability in PC3 human prostate cancer cells is unclear. This study explored whether DADS changed [Ca2+](i) in PC3 cells by using fura-2. DADS at 50-1000 mu M increased [Ca2+](i) in a concentration-dependent manner. The signal was reduced by removing Ca2+. DADS-induced Ca2+ influx was not inhibited by nifedipine. econazole, SK&F96365, and protein kinase C modulators; but was inhibited by aristolochic acid. In Ca2+-free medium, pretreatment with the endoplasmic reticulum Ca2+ pump inhibitors thapsigargin or 2,5-di-tert-butylhydroquinone (BHQ) nearly abolished DADS-induced [Ca2+](i) rise. Incubation with DADS inhibited thapsigargin or BHQ-induced [Ca2+](i), rise. Inhibition of phospholipase C with U73122 did not alter DADS-induced [Ca2+](i) rise. At 500-1000 mu M, DADS killed cells in a concentration-dependent manner. The cytotoxic effect of DADS was partly reversed by prechelating cytosolic Ca2+ with 1,2-bis(2-amino-phenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). Propidium iodide staining suggests that DADS (500 mu M) induced apoptosis in a Ca2+-independent manner. Annexin V/PI staining further shows that 10 mu M and 500 mu M DADS both evoked apoptosis. DADS also increased reactive oxygen species (ROS) production. Collectively, in PC3 cells, DADS induced [Ca2+](i) rise probably by causing phospholipase C-independent Ca2+ release from the endoplasmic reticulum and Ca2+ influx via phospholipase A(2)-sensitive channels. DADS induced Ca2+-dependent cell death, ROS production, and Ca2+-independent apoptosis. (c) 2011 Elsevier Ltd. All rights reserved.