4.2 Article

Effect of celecoxib on Ca2+ handling and viability in human prostate cancer cells (PC3)

Journal

DRUG AND CHEMICAL TOXICOLOGY
Volume 35, Issue 4, Pages 456-462

Publisher

INFORMA HEALTHCARE
DOI: 10.3109/01480545.2011.638927

Keywords

Ca2+; celecoxib; PC3; prostate cancer; thapsigargin

Funding

  1. Kaohsiung Veterans General Hospital [VGHKS99-098, VGHKS99-056]

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Celecoxib has been shown to have an antitumor effect in previous studies, but the mechanisms are unclear. Ca2+ is a key second messenger in most cells. The effect of celecoxib on cytosolic free Ca2+ concentrations ([Ca2+](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 mu M increased [Ca2+](i) in a concentration-dependent manner. The Ca2+ signal was reduced partly by removing extracellular Ca2+. Celecoxib-induced Ca2+ influx was not blocked by L-type Ca2+ 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 Ca2+-free medium, 30 mu M of celecoxib failed to induce a [Ca2+](i) rise after pretreatment with thapsigargin (an endoplasmic reticulum [ER] Ca2+ pump inhibitor). Conversely, pretreatment with celecoxib inhibited thapsigargin-induced Ca2+ release. Inhibition of phospholipase C with U73122 did not change celecoxib-induced [Ca2+](i) rises. Celecoxib induced slight cell death in a concentration-dependent manner, which was enhanced by chelating cytosolic Ca2+ with BAPTA. Collectively, in PC3 cells, celecoxib induced [Ca2+](i) rises by causing phospholipase C-independent Ca2+ release from the ER and Ca2+ influx via non-L-type, phospholipase A(2)-regulated Ca2+ channels. These data may contribute to the understanding of the effect of celecoxib on prostate cancer cells.

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