title: Safrole-induced Ca2+ mobilization and cytotoxicity in human PC3 prostate cancer cells.
abstract: The effect of the carcinogen safrole on intracellular Ca2+ mobilization and on viability of human PC3 prostate cancer cells was examined. Cytosolic free Ca2+ levels ([Ca2+]i) were measured by using fura-2 as a probe. Safrole at concentrations above 10 microM increased [Ca2+]i in a concentration-dependent manner with an EC50 value of 350 microM. The Ca2+ signal was reduced by more than half after removing extracellular Ca2+ but was unaffected by nifedipine, nicardipine, nimodipine, diltiazem, or verapamil. In Ca2+-free medium, after treatment with 650 microM safrole, 1 microM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor) failed to release Ca2+. Neither inhibition of phospholipase C with U73122 nor modulation of protein kinase C activity affected safrole-induced Ca2+ release. Overnight incubation with 0.65-65 microM safrole did not affect cell viability, but incubation with 325-625 microM safrole decreased viability. Collectively, the data suggest that in PC3 cells, safrole induced a [Ca2+]i increase by causing Ca2+ release from the endoplasmic reticulum in a phospholipase C- and protein kinase C-independent fashion, and by inducing Ca2+ influx. Safrole can decrease cell viability in a concentration-dependent manner.
authors.affiliation: Department of Urology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: H C
authors.initials: HC
authors.lastname: Chang
authors.forename: H H
authors.initials: HH
authors.lastname: Cheng
authors.forename: C J
authors.initials: CJ
authors.lastname: Huang
authors.forename: W C
authors.initials: WC
authors.lastname: Chen
authors.forename: I S
authors.initials: IS
authors.lastname: Chen
authors.forename: S I
authors.initials: SI
authors.lastname: Liu
authors.forename: S S
authors.initials: SS
authors.lastname: Hsu
authors.forename: H T
authors.initials: HT
authors.lastname: Chang
authors.forename: J K
authors.initials: JK
authors.lastname: Wang
authors.forename: Y C
authors.initials: YC
authors.lastname: Lu
authors.forename: C T
authors.initials: CT
authors.lastname: Chou
authors.forename: C R
authors.initials: CR
authors.lastname: Jan
mesh_terms: D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects*; D002273:Carcinogens / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D011493:Protein Kinase C / Q000378:metabolism; D012451:Safrole / Q000633:toxicity*; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D002121:Calcium Channel Blockers; D002273:Carcinogens; D011493:Protein Kinase C; D010738:Type C Phospholipases; D012451:Safrole