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

Neurosci Lett. 2008 Sep 12;442(2):109-13. doi: 10.1016/j.neulet.2008.07.014. Epub 2008 Jul 10.


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 (25-100muM) for 24h 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 8h 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Celecoxib
  • Cell Line, Tumor
  • Cyclooxygenase Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glioblastoma / drug therapy
  • Glioblastoma / pathology*
  • Glioblastoma / physiopathology
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins / metabolism*
  • Neoplasm Proteins / metabolism*
  • Pyrazoles / pharmacology*
  • Signal Transduction / drug effects
  • Sulfonamides / pharmacology*
  • Survivin
  • TNF-Related Apoptosis-Inducing Ligand / pharmacology*


  • BIRC5 protein, human
  • Cyclooxygenase Inhibitors
  • Enzyme Inhibitors
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • Pyrazoles
  • Sulfonamides
  • Survivin
  • TNF-Related Apoptosis-Inducing Ligand
  • Celecoxib