title: Effect of diindolylmethane on Ca2+ homeostasis and viability in PC3 human prostate cancer cells.
abstract: The effect of the natural product diindolylmethane on cytosolic Ca(2+) concentrations ([Ca(2+)](i)) and viability in PC3 human prostate cancer cells was explored. The Ca(2+)-sensitive fluorescent dye fura-2 was applied to measure [Ca(2+)](i). Diindolylmethane at concentrations of 20-50 µM induced [Ca(2+)](i) rise in a concentration-dependent manner. The response was reduced partly by removing Ca(2+). Diindolylmethane-evoked Ca(2+) entry was suppressed by nifedipine, econazole, SK&F96365, protein kinase C modulators and aristolochic acid. In the absence of extracellular Ca(2+), incubation with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin or 2,5-di-tert-butylhydroquinone (BHQ) inhibited or abolished diindolylmethane-induced [Ca(2+)](i) rise. Incubation with diindolylmethane also inhibited thapsigargin or BHQ-induced [Ca(2+)](i) rise. Inhibition of phospholipase C with U73122 reduced diindolylmethane-induced [Ca(2+)](i) rise. At concentrations of 50-100 µM, diindolylmethane killed cells in a concentration-dependent manner. This cytotoxic effect was not altered by chelating cytosolic Ca(2+) with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). Annexin V/PI staining data implicate that diindolylmethane (50 and 100 µM) induced apoptosis in a concentration-dependent manner. In conclusion, diindolylmethane induced a [Ca(2+)](i) rise in PC3 cells by evoking phospholipase C-dependent Ca(2+) release from the endoplasmic reticulum and Ca(2+) entry via phospholipase A(2)-sensitive store-operated Ca(2+) channels. Diindolylmethane caused cell death in which apoptosis may participate.
authors: Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors: Jeng-Yu
authors: JY
authors: Tsai
authors: Chiang-Ting
authors: CT
authors: Chou
authors: Shuih-Inn
authors: SI
authors: Liu
authors: Wei-Zhe
authors: WZ
authors: Liang
authors: Chun-Chi
authors: CC
authors: Kuo
authors: Wei-Chuan
authors: WC
authors: Liao
authors: Ko-Long
authors: KL
authors: Lin
authors: Shu-Shong
authors: SS
authors: Hsu
authors: Yi-Chau
authors: YC
authors: Lu
authors: Jong-Khing
authors: JK
authors: Huang
authors: Chung-Ren
authors: CR
authors: Jan
mesh_terms: D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D016257:Fura-2 / Q000494:pharmacology; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism*; D019284:Thapsigargin / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D007211:Indoles; D019284:Thapsigargin; D010738:Type C Phospholipases; C016392:3,3'-diindolylmethane; D002118:Calcium; D016257:Fura-2