Elsevier

Neuroscience Letters

Volume 442, Issue 2, 12 September 2008, Pages 109-113
Neuroscience Letters

TRAIL-mediated apoptosis in malignant glioma cells is augmented by celecoxib through proteasomal degradation of survivin

https://doi.org/10.1016/j.neulet.2008.07.014Get rights and content

Abstract

Celecoxib is a cyclooxygenase 2-selective nonsteroidal anti-inflammatory drug (NSAID) that exhibited therapeutic activity in cancer. In this study three malignant glioma, U87-MG, U251 and A172, were treated with celecoxib, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) or the combination of both. Single treatment with celecoxib (25–100 μM) for 24 h resulted in a concentration-dependant decrease of cellular viability in U87-MG, U251 and A172. Combining subtoxic concentrations of celecoxib with TRAIL strongly increased cell death in human malignant glioma cells. After 8 h treatment with celecoxib we found down-regulation of the inhibitor of apoptosis protein survivin that was mediated by proteasomal degradation. In addition, over-expression of survivin not only attenuated celecoxib-induced cytotoxicity but also cytotoxicity induced by the combination of celecoxib and TRAIL. Taken together, in malignant glioma survivin is a key regulator in celecoxib- and TRAIL–celecoxib-mediated cell death.

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Acknowledgements

This work was supported by grants from the Post-Doc Program of the University of Heidelberg to Dr. med. Markus David Siegelin. The plasmid pcDNA3-survivin was kindly provided by Dr. Dario Altieri.

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