Celecoxib Increased Expression of 14-3-3 Sigma and Induced Apoptosis of Glioma Cells

Abstract

Background: Celecoxib, a cyclooxygenase-2 inhibitor has been found to inhibit the proliferation of several kinds of cancer cells: however, the effects of celecoxib on glioma cells are not clear. Materials and Methods: A172 glioma cells were treated with various concentrations of celecoxib for 4, 24 or 48 h. Cytotoxic drug effects were studied by MTT (3-[4,5- dimethylthiazole-2-yl]-2,5- diphenyltetrazolium bromide)-based colorimetric assay, and celecoxib-induced apoptosis of glioma cells was investigated by FACScan. Western blot analysis was used to study celecoxib effects on the expression of mitogen-activated protein kinases (MAPKs) , p53, p21, 14-3-4 sigma, Bcl-2 and Bax. Caspace-3 activity in glioma cells was analyzed by caspase activity assay. Results: Celecoxib exerted cytotoxic effects upon and induced apoptosis of the A172 glioma cells in a concentration and time-dependent manner (p<0.05). Celecoxib had no effects on expression of MAPKs, Bax, or p21; however, it increased expression of p53 and 14-3-4 sigma, and reduced expression of Bcl-2. Celecoxib also increased the activity of caspace-3 in glioma cells. The apoptotic fraction of A 172 cells induced by 24-h treatment with 100 mu M celecoxib was reduced from 39% to 23% by pretreatment wi. th caspace-3 inhibitor (DEVD-CHO) (p<0.001). Conclusion: The results suggest that celecoxib induced cytotoxicity and apoptosis in this line of glioma cells and that such effects might be related to activation of p53 and 14-3-3 sigma, reduced Bcl-2 and Bcl-2/Bax ratio, and increased caspace-3 activiy.