title: Effect of diallyl disulfide on Ca2+ movement and viability in PC3 human prostate cancer cells.
abstract: The effect of diallyl disulfide (DADS) on cytosolic Ca(2+) concentrations ([Ca(2+)](i)) and viability in PC3 human prostate cancer cells is unclear. This study explored whether DADS changed [Ca(2+)](i) in PC3 cells by using fura-2. DADS at 50-1000 μM increased [Ca(2+)](i) in a concentration-dependent manner. The signal was reduced by removing Ca(2+). DADS-induced Ca(2+) influx was not inhibited by nifedipine, econazole, SK&F96365, and protein kinase C modulators; but was inhibited by aristolochic acid. In Ca(2+)-free medium, pretreatment with the endoplasmic reticulum Ca(2+) pump inhibitors thapsigargin or 2,5-di-tert-butylhydroquinone (BHQ) nearly abolished DADS-induced [Ca(2+)](i) rise. Incubation with DADS inhibited thapsigargin or BHQ-induced [Ca(2+)](i) rise. Inhibition of phospholipase C with U73122 did not alter DADS-induced [Ca(2+)](i) rise. At 500-1000 μM, DADS killed cells in a concentration-dependent manner. The cytotoxic effect of DADS was partly reversed by prechelating cytosolic Ca(2+) with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). Propidium iodide staining suggests that DADS (500 μM) induced apoptosis in a Ca(2+)-independent manner. Annexin V/PI staining further shows that 10 μM and 500 μM DADS both evoked apoptosis. DADS also increased reactive oxygen species (ROS) production. Collectively, in PC3 cells, DADS induced [Ca(2+)](i) rise probably by causing phospholipase C-independent Ca(2+) release from the endoplasmic reticulum and Ca(2+) influx via phospholipase A(2)-sensitive channels. DADS induced Ca(2+)-dependent cell death, ROS production, and Ca(2+)-independent apoptosis.
authors.affiliation: Department of Surgery, Ping Tung Christian Hospital, Ping Tung 900, Taiwan.
authors.forename: Wei-Chuan
authors.initials: WC
authors.lastname: Chen
authors.forename: Shu-Shong
authors.initials: SS
authors.lastname: Hsu
authors.forename: Chiang-Ting
authors.initials: CT
authors.lastname: Chou
authors.forename: Chun-Chi
authors.initials: CC
authors.lastname: Kuo
authors.forename: Jong-Khing
authors.initials: JK
authors.lastname: Huang
authors.forename: Yi-Chien
authors.initials: YC
authors.lastname: Fang
authors.forename: Hong-Tai
authors.initials: HT
authors.lastname: Chang
authors.forename: Jeng-Yu
authors.initials: JY
authors.lastname: Tsai
authors.forename: Wei-Chuan
authors.initials: WC
authors.lastname: Liao
authors.forename: Being-Whey
authors.initials: BW
authors.lastname: Wang
authors.forename: Pochuen
authors.initials: P
authors.lastname: Shieh
authors.forename: Daih-Huang
authors.initials: DH
authors.lastname: Kuo
authors.forename: Chung-Ren
authors.initials: CR
authors.lastname: Jan
mesh_terms: D000498:Allyl Compounds / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004220:Disulfides / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D016257:Fura-2 / Q000737:chemistry; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000498:Allyl Compounds; D000970:Antineoplastic Agents; D004220:Disulfides; D017382:Reactive Oxygen Species; C028009:diallyl disulfide; D002118:Calcium; D016257:Fura-2