Celecoxib increased expression of 14-3-3σ and induced apoptosis of glioma cells
Journal
Anticancer Research
Journal Volume
27
Journal Issue
4 B
Pages
2547-2554
Date Issued
2007
Author(s)
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, 14-3-4σ, Bcl-2 and Box. 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, Box, or p21; however, it increased expression of p53 and 14-3-4σ, and reduced expression of Bcl-2. Celecoxib also increased the activity of caspace-3 in glioma cells. The apoptotic fraction of A172 cells induced by 24-h treatment with 100 μM celecoxib was reduced from 39% to 23% by pretreatment with 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 14-3-3σ, reduced Bcl-2 and Bcl-2/Bax ratio, and increased caspace-3 activity.
Subjects
Apoptosis; Celecoxib; Cytotoxicity; Glioma cells
SDGs
Other Subjects
3 (4,5 dimethyl 2 thiazolyl) 2,5 diphenyltetrazolium bromide; caspase 3; caspase 3 inhibitor; celecoxib; mitogen activated protein kinase; protein; protein 14 3 4sigma; protein Bax; protein bcl 2; protein p21; protein p53; unclassified drug; animal cell; apoptosis; article; colorimetry; concentration response; controlled study; cytotoxicity; drug effect; drug mechanism; enzyme activity; fluorescence activated cell sorting; glioma cell; nonhuman; priority journal; protein expression; rat; Western blotting; 14-3-3 Proteins; Animals; Apoptosis; bcl-2-Associated X Protein; Caspase 3; Cell Division; Cyclin-Dependent Kinase Inhibitor p21; Cyclooxygenase 2; G2 Phase; Glioma; Mitogen-Activated Protein Kinases; Proto-Oncogene Proteins c-bcl-2; Pyrazoles; Rats; Sulfonamides; Tumor Suppressor Protein p53
Type
journal article