title: Effect of capsazepine on cytosolic Ca(2+) levels and proliferation of human prostate cancer cells.
abstract: Capsazepine has been widely used as a selective antagonist of vanilloid type 1 receptors; however, its other in vitro effect on most cell types is unknown. In human PC3 prostate cancer cells, the effect of capsazepine on intracellular Ca(2+) concentrations ([Ca(2+)](i)) and cytotoxicity was investigated by using fura-2 and tetrazolium, respectively. Capsazepine caused a rapid rise in [Ca(2+)](i) in a concentration-dependent manner with an EC(50) value of 75 microM. Capsazepine-induced [Ca(2+)](i) rise was reduced by 60% by removal of extracellular Ca(2+), suggesting that the capsazepine-induced [Ca(2+)](i) rise was contributed by extracellular Ca(2+) influx and intracellular Ca(2+). Consistently, the capsazepine (200 microM)-induced [Ca(2+)](i) rise was decreased by La(3+) by half. In Ca(2+)-free medium, thapsigargin, an inhibitor of the endoplasmic reticulum Ca(2+)-ATPase, caused a monophasic [Ca(2+)](i) rise, after which the effect of capsazepine on [Ca(2+)](i) was inhibited by 80%. Conversely, pretreatment with capsazepine partly reduced thapsigargin-induced [Ca(2+)](i) rise. U73122, an inhibitor of phospholipase C, abolished histamine (an inositol 1,4,5-trisphosphate-dependent Ca(2+) mobilizer)-induced, but not capsazepine-induced, [Ca(2+)](i) rise. These findings suggest that in human PC3 prostate cancer cells, capsazepine increases [Ca(2+)](i) by evoking Ca(2+) influx and releasing Ca(2+) from the endoplasmic reticulum via a phospholiase C-independent manner. Overnight incubation with capsazepine (200 microM) killed 37% of cells, which could not be prevented by chelating intracellular Ca(2+) with BAPTA.
authors.affiliation: Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan.
authors.forename: Jong-Khing
authors.initials: JK
authors.lastname: Huang
authors.forename: He-Hsiung
authors.initials: HH
authors.lastname: Cheng
authors.forename: Chun-Jen
authors.initials: CJ
authors.lastname: Huang
authors.forename: Chun-Chi
authors.initials: CC
authors.lastname: Kuo
authors.forename: Wei-Chuan
authors.initials: WC
authors.lastname: Chen
authors.forename: Shiuh-Inn
authors.initials: SI
authors.lastname: Liu
authors.forename: Shu-Shong
authors.initials: SS
authors.lastname: Hsu
authors.forename: Hong-Tai
authors.initials: HT
authors.lastname: Chang
authors.forename: Yih-Chau
authors.initials: YC
authors.lastname: Lu
authors.forename: Li-Ling
authors.initials: LL
authors.lastname: Tseng
authors.forename: An-Jen
authors.initials: AJ
authors.lastname: Chiang
authors.forename: Chiang-Ting
authors.initials: CT
authors.lastname: Chou
authors.forename: Chung-Ren
authors.initials: CR
authors.lastname: Jan
mesh_terms: D002118:Calcium / Q000378:metabolism*; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003600:Cytosol / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors*; D010738:Type C Phospholipases / Q000502:physiology
chemical_list: D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D004533:Egtazic Acid; D010738:Type C Phospholipases; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; C071423:capsazepine; D002211:Capsaicin; D002118:Calcium