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

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• 作者：Wei-Chuan Chen^a ; Shu-Shong Hsu^b ; Chiang-Ting Chou^c ; ^d ; Chun-Chi Kuo^e ; Jong-Khing Huang^b ; Yi-Chien Fang^f ; Hong-Tai Chang^b ; Jeng-Yu Tsai^b ; Wei-Chuan Liao^b ; ^g ; Being-Whey Wang^b ; Pochuen Shieh^h ; Daih-Huang Kuo^h ; Chung-Ren Janⁱ ; ^{crjan@isca.vghks.gov.tw}
• 关键词：Ca²⁺ ; Diallyl disulfide ; PC3 ; Prostate
• 刊名：Toxicology in Vitro
• 出版年：2011
• 出版时间：April 2011
• 年：2011
• 卷：25
• 期：3
• 页码：636-643
• 全文大小：489 K

文摘

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 μM 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 μM, 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-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA). Propidium iodide staining suggests that DADS (500 μM) induced apoptosis in a Ca²⁺-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 [Ca²⁺]_i rise probably by causing phospholipase C-independent Ca²⁺ release from the endoplasmic reticulum and Ca²⁺ influx via phospholipase A₂-sensitive channels. DADS induced Ca²⁺-dependent cell death, ROS production, and Ca²⁺-independent apoptosis.