title: Mechanisms of resveratrol-induced changes in cytosolic free calcium ion concentrations and cell viability in OC2 human oral cancer cells.
abstract: Resveratrol is a natural compound that affects cellular calcium (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 OC2 human oral cancer cells. The Ca(2+)-sensitive fluorescent dye fura-2 was used to measure [Ca(2+)]i, and water-soluble tetrazolium-1 was used to measure viability. Resveratrol evoked concentration-dependent increase in [Ca(2+)]i. The response was reduced by removing extracellular Ca(2+). Resveratrol also caused manganese-induced fura-2 fluorescence quench. Resveratrol-evoked Ca(2+) entry was inhibited by nifedipine and the protein kinase C (PKC) inhibitor GF109203X but was not altered by econazole, SKF96365, and the PKC 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 (BHQ) abolished resveratrol-evoked [Ca(2+)]i rise. Conversely, treatment with resveratrol inhibited BHQ-evoked [Ca(2+)]i rise. Inhibition of phospholipase C (PLC) with U73122 abolished resveratrol-evoked [Ca(2+)]i rise. At 20-100 μM, resveratrol decreased cell viability, which was not affected by chelating cytosolic Ca(2+)with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester. Annexin V-fluorescein isothiocyanate staining data suggest that resveratrol at 20-40 μM induced apoptosis in a concentration-dependent manner. Collectively, in OC2 cells, resveratrol induced [Ca(2+)]i rise by evoking PLC-dependent Ca(2+) release from the endoplasmic reticulum and by causing Ca(2+) entry via nifedipine-sensitive, PKC-regulated mechanisms. Resveratrol also caused Ca(2+)-independent apoptosis.
authors.affiliation: Department of Dentistry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: H-J
authors.initials: HJ
authors.lastname: Chang
authors.affiliation: Department of Nursing, Division of Basic Medical Sciences, Chang Gung University of Science and Technology, Chia-Yi, Taiwan Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Chia-Yi, Taiwan.
authors.forename: C-T
authors.initials: CT
authors.lastname: Chou
authors.affiliation: Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan College of Management, National Sun Yat-sen University, Kaohsiung, Taiwan.
authors.forename: H-T
authors.initials: HT
authors.lastname: Chang
authors.affiliation: Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: W-Z
authors.initials: WZ
authors.lastname: Liang
authors.affiliation: Department of Laboratory Medicine, Zuoying Armed Forces General Hospital, Kaohsiung, Taiwan.
authors.forename: T-Y
authors.initials: TY
authors.lastname: Hung
authors.affiliation: Department of Laboratory Medicine, Zuoying Armed Forces General Hospital, Kaohsiung, Taiwan.
authors.forename: Y-D
authors.initials: YD
authors.lastname: Li
authors.affiliation: Department of Laboratory Medicine, Zuoying Armed Forces General Hospital, Kaohsiung, Taiwan.
authors.forename: Y-C
authors.initials: YC
authors.lastname: Fang
authors.affiliation: Department of Nursing, Tzu Hui Institute of Technology, Pingtung, Taiwan.
authors.forename: C-C
authors.initials: CC
authors.lastname: Kuo
authors.affiliation: Department of Pharmacy, Tajen University, Pingtung, Taiwan.
authors.forename: D-H
authors.initials: DH
authors.lastname: Kuo
authors.affiliation: Department of Pharmacy, Tajen University, Pingtung, Taiwan.
authors.forename: P
authors.initials: P
authors.lastname: Shieh
authors.affiliation: Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan crjan@isca.vghks.gov.tw.
authors.forename: C-R
authors.initials: CR
authors.lastname: Jan
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D009062:Mouth Neoplasms; D011493:Protein Kinase C / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D013267:Stilbenes; D011493:Protein Kinase C; D010738:Type C Phospholipases; D000077185:Resveratrol; D002118:Calcium
keywords: Ca2+; fura-2; human oral cancer cells; resveratrol