title: Mechanisms of resveratrol-induced changes in [Ca(2+)]i and cell viability in PC3 human prostate cancer cells.
abstract: Resveratrol is a natural compound that affects cellular Ca(2+) homeostasis and viability in different cells. This study examined the effect of resveratrol on cytosolic free Ca(2+) concentrations ([Ca(2+)]i) and viability in PC3 human prostate cancer cells. The Ca(2+)-sensitive fluorescent dye fura-2 was used to measure [Ca(2+)]i and WST-1 was used to measure viability. Resveratrol-evoked [Ca(2+)]i rises concentration-dependently. The response was reduced by removing extracellular Ca(2+). Resveratrol-evoked Ca(2+) entry was not inhibited by nifedipine, econazole, SKF96365 and the protein kinase C inhibitor GF109203X, but was nearly abolished by the protein kinase C activator phorbol 12-myristate 13 acetate. In Ca(2+)-free medium, treatment with the endoplasmic reticulum Ca(2+) pump inhibitor 2,5-di-tert-butylhydroquinone decreased resveratrol-evoked rise in [Ca(2+)]i. Conversely, treatment with resveratrol inhibited BHQ-evoked rise in [Ca(2+)]i. Inhibition of phospholipase C with U73122 did not alter resveratrol-evoked rise in [Ca(2+)]i. Previous studies showed that resveratrol between 10 and 100 µM induced cell death in various cancer cell types including PC3 cells. However, in this study, resveratrol (1-10 μM) increased cell viability, which was abolished by chelating cytosolic Ca(2+) with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid-acetoxymethyl ester (BAPTA/AM). Therefore, it is suggested that in PC3 cells, resveratrol had a dual effect on viability: at low concentrations (1-10 µM) it induced proliferation, whereas at higher concentrations it caused cell death. Collectively, our data suggest that in PC3 cells, resveratrol-induced rise in [Ca(2+)]i by evoking phospholipase C-independent Ca(2+) release from the endoplasmic reticulum and Ca(2+) entry, via protein kinase C-regulated mechanisms. Resveratrol at 1-10 µM also caused Ca(2+)-dependent cell proliferation.
authors.affiliation: Department of Surgery, Kaohsiung Veterans General Hospital , Kaohsiung , Taiwan .
authors.forename: Hong-Tai
authors.initials: HT
authors.lastname: Chang
authors.forename: Chiang-Ting
authors.initials: CT
authors.lastname: Chou
authors.forename: I-Li
authors.initials: IL
authors.lastname: Chen
authors.forename: Wei-Zhe
authors.initials: WZ
authors.lastname: Liang
authors.forename: Daih-Huang
authors.initials: DH
authors.lastname: Kuo
authors.forename: Jong-Khing
authors.initials: JK
authors.lastname: Huang
authors.forename: Pochuen
authors.initials: P
authors.lastname: Shieh
authors.forename: Chung-Ren
authors.initials: CR
authors.lastname: Jan
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D008297:Male; D010704:Phorbols / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage*
chemical_list: D010704:Phorbols; D047428:Protein Kinase Inhibitors; D013267:Stilbenes; D011493:Protein Kinase C; D000077185:Resveratrol; D002118:Calcium; C033085:phorbol