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Celecoxib induces apoptosis by inhibiting the expression of survivin in HeLa cells
Authors:Fukada Kazuhiro  Takahashi-Yanaga Fumi  Sakoguchi-Okada Naoko  Shiraishi Fumie  Miwa Yoshikazu  Morimoto Sachio  Sasaguri Toshiyuki
Affiliation:Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
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.
Keywords:Clecoxib   Survivin   Promoter activity   Apoptosis   Cancer   Nonsteroidal anti-inflammatory drugs (NSAIDs)
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