title: Effect of celecoxib on Ca(2+) handling and viability in human prostate cancer cells (PC3).
abstract: Celecoxib has been shown to have an antitumor effect in previous studies, but the mechanisms are unclear. Ca(2+) is a key second messenger in most cells. The effect of celecoxib on cytosolic free Ca(2+) concentrations ([Ca(2+)](i)) in human suspended PC3 prostate cancer cells was explored by using fura-2 as a fluorescent dye. Celecoxib at concentrations between 5 and 30 μM increased [Ca(2+)](i) in a concentration-dependent manner. The Ca(2+) signal was reduced partly by removing extracellular Ca(2+). Celecoxib-induced Ca(2+) influx was not blocked by L-type Ca(2+) entry inhibitors or protein kinase C/A modulators [phorbol 12-myristate 13-acetate (PMA), GF109203X, H-89], but was inhibited by the phospholipase A(2) inhibitor, aristolochic acid. In Ca(2+)-free medium, 30 μM of celecoxib failed to induce a [Ca(2+)](i) rise after pretreatment with thapsigargin (an endoplasmic reticulum [ER] Ca(2+) pump inhibitor). Conversely, pretreatment with celecoxib inhibited thapsigargin-induced Ca(2+) release. Inhibition of phospholipase C with U73122 did not change celecoxib-induced [Ca(2+)](i) rises. Celecoxib induced slight cell death in a concentration-dependent manner, which was enhanced by chelating cytosolic Ca(2+) with BAPTA. Collectively, in PC3 cells, celecoxib induced [Ca(2+)](i) rises by causing phospholipase C-independent Ca(2+) release from the ER and Ca(2+) influx via non-L-type, phospholipase A(2)-regulated Ca(2+) channels. These data may contribute to the understanding of the effect of celecoxib on prostate cancer cells.
authors.affiliation: Department of Rehabilitation, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Jue-Long
authors.initials: JL
authors.lastname: Wang
authors.forename: Ko-Long
authors.initials: KL
authors.lastname: Lin
authors.forename: Chiang-Ting
authors.initials: CT
authors.lastname: Chou
authors.forename: Chun-Chi
authors.initials: CC
authors.lastname: Kuo
authors.forename: Jin-Shiung
authors.initials: JS
authors.lastname: Cheng
authors.forename: Shu-Shong
authors.initials: SS
authors.lastname: Hsu
authors.forename: Hong-Tai
authors.initials: HT
authors.lastname: Chang
authors.forename: Jeng-Yu
authors.initials: JY
authors.lastname: Tsai
authors.forename: Wei-Chuan
authors.initials: WC
authors.lastname: Liao
authors.forename: Yi-Chau
authors.initials: YC
authors.lastname: Lu
authors.forename: I-Shu
authors.initials: IS
authors.lastname: Chen
authors.forename: Shuih-Inn
authors.initials: SI
authors.lastname: Liu
authors.forename: Chung-Ren
authors.initials: CR
authors.lastname: Jan
mesh_terms: D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism; D000068579:Celecoxib; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005456:Fluorescent Dyes / Q000737:chemistry; D016257:Fura-2 / Q000737:chemistry; D006801:Humans; D008297:Male; D054467:Phospholipases A2 / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology*; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D020746:Calcium Channels, L-Type; D052246:Cyclooxygenase 2 Inhibitors; D005456:Fluorescent Dyes; D011720:Pyrazoles; D013449:Sulfonamides; D054467:Phospholipases A2; D000068579:Celecoxib; D002118:Calcium; D016257:Fura-2