Celecoxib induces apoptosis by inhibiting the expression of survivin in HeLa cells.
The effect of celecoxib, a cyclooxygenase-2 selective inhibitor, on a human cervical cancer cell line, HeLa cells, was examined. We found that celecoxib increased DNA ladder formation and the activity of caspase-3, indicating that celecoxib induced apoptosis in HeLa cells. Celecoxib suppressed the expression of an anti-apoptotic protein, survivin, in both protein and mRNA levels. The overexpression of survivin overrode caspase-3 activation induced by celecoxib. Subsequently, we performed luciferase reporter assay with the reporter vector containing human survivin promoter region and electrophoretic mobility shift assay and found that the -75 to -66 bp region relative to the initiating codon played an important role in celecoxib action to suppress survivin promoter activity. Our findings might provide a new insight into the anti-cancer effects of celecoxib.
Fukada
Kazuhiro
K
Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Takahashi-Yanaga
Fumi
F
Sakoguchi-Okada
Naoko
N
Shiraishi
Fumie
F
Miwa
Yoshikazu
Y
Morimoto
Sachio
S
Sasaguri
Toshiyuki
T
D017209:Apoptosis / Q000187:drug effects*; D000068579:Celecoxib; D015870:Gene Expression / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D011720:Pyrazoles / Q000008:administration & dosage*; D015398:Signal Transduction / Q000187:drug effects*; D013449:Sulfonamides / Q000008:administration & dosage*; D000077022:Survivin
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D011720:Pyrazoles; D013449:Sulfonamides; D000077022:Survivin; D000068579:Celecoxib