title: Celecoxib induces apoptosis by inhibiting the expression of survivin in HeLa cells.
abstract: 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.
authors.affiliation: Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Fukada
authors.forename: Fumi
authors.initials: F
authors.lastname: Takahashi-Yanaga
authors.forename: Naoko
authors.initials: N
authors.lastname: Sakoguchi-Okada
authors.forename: Fumie
authors.initials: F
authors.lastname: Shiraishi
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Miwa
authors.forename: Sachio
authors.initials: S
authors.lastname: Morimoto
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Sasaguri
mesh_terms: 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
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D011720:Pyrazoles; D013449:Sulfonamides; D000077022:Survivin; D000068579:Celecoxib