Celecoxib increased expression of 14-3-3sigma and induced apoptosis of glioma cells.
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.


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, 14-3-4sigma, 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 14-3-4sigma, 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 microM celecoxib was reduced from 39% to 23% by pretreatment with caspace-3 inhibitor (DEVD-CHO) (p < 0.001).


CONCLUSIONS
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 14-3-3sigma, reduced Bcl-2 and Bcl-2/Bax ratio, and increased caspace-3 activity.
Chen
Jin-Cherng
JC
Department of Surgery, Buddhist Tzu Chi Dalin General Hospital, 2, Ming Shen Road, Dalin, Chia-Yi, ROC.
Chen
Yun
Y
Su
Yen-Hao
YH
Tseng
Sheng-Hong
SH
D048948:14-3-3 Proteins / Q000096:biosynthesis*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D061945:Caspase Inhibitors; D000068579:Celecoxib; D002455:Cell Division / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D016195:G2 Phase / Q000187:drug effects; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020928:Mitogen-Activated Protein Kinases / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D013449:Sulfonamides / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
D048948:14-3-3 Proteins; C494828:Bax protein, rat; D061945:Caspase Inhibitors; D050759:Cyclin-Dependent Kinase Inhibitor p21; D019253:Proto-Oncogene Proteins c-bcl-2; D011720:Pyrazoles; C519988:Sfn protein, rat; D013449:Sulfonamides; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases; D053148:Caspase 3; D000068579:Celecoxib