title: Celecoxib-induced increase in cytosolic Ca(2+) levels and apoptosis in HA59T human hepatoma cells.
abstract: Celecoxib has been shown to have antitumor effect in previous studies but the mechanisms are unclear. The effect of celecoxib on cytosolic Ca(2+) concentrations ([Ca(2+)]i) and viability in HA59T human hepatoma cells was explored. The Ca(2+)-sensitive fluorescent dye fura-2 was applied to measure [Ca(2+)]i. Celecoxib at concentrations of 10-50 μM induced a [Ca(2+)]i rise in a concentration-dependent manner. The response was reduced by 80% by removing Ca(2+). Celecoxib induced Mn(2+) influx, leading to quenching of fura-2 fluorescence. Celecoxib-evoked Ca(2+) entry was suppressed by nifedipine, econazole, SK&F96365, and protein kinase C modulators. In the absence of extracellular Ca(2+), incubation with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin nearly abolished celecoxib-induced [Ca(2+)]i rise. Incubation with celecoxib abolished thapsigargin-induced [Ca(2+)]i rise. Inhibition of phospholipase C with U73122 abolished celecoxib-induced [Ca(2+)]i rise. At 1-50 μM, celecoxib inhibited cell viability by less than 20%, which was not reversed by chelating cytosolic Ca(2+) with 1,2-bis(2-aminophenoxy)ethane-N, N, N', N'-tetraacetic acid/acetoxy methyl (BAPTA/AM). Celecoxib (10-50 μM) also induced apoptosis. In sum, in HA59T hepatoma cells, celecoxib induced a [Ca(2+)]i rise by evoking phospholipase C-dependent Ca(2+) release from the endoplasmic reticulum and Ca(2+) entry via protein kinase C-sensitive store-operated Ca(2+) channels. Celecoxib also caused cell death via apoptosis.
authors: Department of Medicine, Chang Bing Show Chwan Memorial Hospital, Changhua County, Taiwan.
authors: H-H
authors: HH
authors: Cheng
authors: 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: C-T
authors: CT
authors: Chou
authors: Department of Orthopedics, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors: Y-C
authors: YC
authors: Lu
authors: Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors: T
authors: T
authors: Lu
authors: Department of Otolaryngology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors: C-C
authors: CC
authors: Chi
authors: Department of Dentistry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors: L-L
authors: LL
authors: Tseng
authors: Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors: S-I
authors: SI
authors: Liu
authors: Department of Medicine, Yongkang Veterans Hospital, Tainan, Taiwan.
authors: J-S
authors: JS
authors: Cheng
authors: Institute of Nursing and Department of Nursing, Chang Gung Institute of Technology Chiayi Campus, Taiwan.
authors: C-C
authors: CC
authors: Kuo
authors: Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors: W-Z
authors: WZ
authors: Liang
authors: Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan crjan@isca.vghks.gov.tw.
authors: C-R
authors: CR
authors: Jan
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular; D000068579:Celecoxib; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms; D011493:Protein Kinase C / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D011493:Protein Kinase C; D010738:Type C Phospholipases; D000068579:Celecoxib; D002118:Calcium
keywords: Ca2+; HA59 T; celecoxib; hepatoma cells