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Journal of Neuro-Oncology

, Volume 106, Issue 1, pp 99–109 | Cite as

The nonsteroidal anti-inflammatory drug celecoxib suppresses the growth and induces apoptosis of human glioblastoma cells via the NF-κB pathway

  • Gangadhara Reddy Sareddy
  • Khamushavalli Geeviman
  • Chinta Ramulu
  • Phanithi Prakash Babu
Laboratory Investigation - Human/Animal Tissue

Abstract

Gliomas are devastating primary tumors of the central nervous system and tend to recur even after standard therapy. Celecoxib, the selective COX-2 nonsteroidal anti-inflammatory drug, has anti-neoplastic activity against several malignancies. Accumulating evidence suggests that several COX-2-independent mechanisms may also be involved in the anti-tumor effects of celecoxib. Deregulation of the NF-κB signaling pathway contributes to enhanced glioma cell survival, proliferation, and chemoresistance. In this study, we examined the efficacy of celecoxib in suppressing the growth of glioblastoma cell lines. We observed that treatment with celecoxib significantly reduced the proliferation of a variety of GBM cell lines in a dose-dependent manner and also induced apoptosis, which was evident from enhanced caspase-3 and 8 activity, PARP cleavage, and TUNEL positive cells. Celecoxib treatment significantly down-regulated TNF-α induced NF-κB nuclear translocation, NF-κB DNA binding activity, and NF-κB-dependent reporter gene expression in U373 and T98G cells in a dose-dependent manner. Furthermore, celecoxib suppressed IκBα degradation and phosphorylation and reduced IKK activity in a dose-dependent manner. This study provides evidence that celecoxib suppresses the growth of GBM cell lines partly by inhibiting the NF-κB signaling pathway.

Keywords

Celecoxib NF-κB Glioblastoma p50 p65 IKK IκBα 

Notes

Acknowledgments

We greatly acknowledge the Professor P. Reddanna (University of Hyderabad, India) for providing celecoxib. DBT, DST, CSIR, and ICMR are acknowledged for funding the laboratory, and CSIR, New Delhi, India (fellowship to GRS) is also acknowledged. We acknowledge Dr Syed Maqbool Ahmed, in charge of the CIL facility, UoH, and technical assistance of Miss Nalini for the confocal microscopy.

Supplementary material

11060_2011_662_MOESM1_ESM.tif (169 kb)
Supplementary Fig. 1 Effect of celecoxib on apoptosis of GBM cells. U373 (a) and T98G (b) cells were seeded in chamber plates and treated with vehicle (0.1% DMSO) or the indicated concentrations of celecoxib for 12 h. The cells were then subjected to TUNEL assay as described in the Materials and methods section. DAPI was used to identify nuclei, and data are representative of three independent experiments

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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Gangadhara Reddy Sareddy
    • 1
  • Khamushavalli Geeviman
    • 1
  • Chinta Ramulu
    • 1
  • Phanithi Prakash Babu
    • 1
  1. 1.Department of Biotechnology, School of Life SciencesUniversity of HyderabadHyderabadIndia

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