Biochemical and Biophysical Research Communications, Vol.357, No.4, 1166-1171, 2007
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. (c) 2007 Elsevier Inc. All rights reserved.
Keywords:clecoxib;survivin;promoter activity;apoptosis;cancer;nonsteroidal anti-inflammatory drugs (NSAIDs)