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