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

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 μM increased [Ca²]i in a concentration-dependent manner. The Ca² signal was reduced partly by removing extracellular Ca ². 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 A2 inhibitor, aristolochic acid. In Ca²-free medium, 30 μM 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 Cindependent Ca² release from the ER and Ca² influx via non-L-type, phospholipase A2-regulated Ca² channels. These data may contribute to the understanding of the effect of celecoxib on prostate cancer cells.