The inhibitory effect of celecoxib on mouse hepatoma H22 cell line on the arachidonic acid metabolic pathway

Celecoxib is a selective inhibitor of cyclooxygenase-2 (COX-2) It may reduce the risk of cancer formation by affecting the metabolism of arachidonic acid (AA), which has been implicated in the development of cancer Accordingly, this study was designed to determine the effects of celecoxib on the AA pathway in mouse hepatoma H22 cells. Celecoxib was found to inhibit the proliferation of H22 cells in a dose- and time-dependent manner. Low doses (50 and 100 mu mol.L-1) of celecoxib caused an increase in the expression of cytosolic phospholipase A(2) (cPLA(2)), but did not affect the expression of COX-2 in terms of the mRNA and protein levels. Surprisingly, the amount of AA was elevated and the level of prostaglandin E-2 (PGE(2)) was unaltered in the culture supernatant At higher celecoxib doses (200 and 400 mu mol L-1). the mRNA and protein of both COX-2 and cPLA(2) were inhibited. The concentration of AA was increased. and PGE(2) level was depressed in H22 cells. The ratio of AA to PGE(2) was increased in a dose-dependent manner Our findings suggest that the imbalance between AA and PGE(2) characterized by increased AA at a low dosage and decreased PGE(2) at a high dosage of celecoxib, was an important indicator of cytotoxicity of celecoxib on H22 cells