gms | German Medical Science

61st Annual Meeting of the German Society of Neurosurgery (DGNC) as part of the Neurowoche 2010
Joint Meeting with the Brazilian Society of Neurosurgery on the 20 September 2010

German Society of Neurosurgery (DGNC)

21 - 25 September 2010, Mannheim

Enhancement of the growth-inhibitory effect of temozolomide by the nitric oxide donor PABA/NO in U87 glioma cells in vitro

Meeting Abstract

Search Medline for

  • Evangelos Kogias - Abteilung fr Allgemeine Neurochirurgie, Uniklinik Freiburg, Deutschland
  • Brunhilde Baumer - Abteilung fr Allgemeine Neurochirurgie, Uniklinik Freiburg, Deutschland
  • Astrid Weyerbrock - Abteilung fr Allgemeine Neurochirurgie, Uniklinik Freiburg, Deutschland

Deutsche Gesellschaft fr Neurochirurgie. 61. Jahrestagung der Deutschen Gesellschaft fr Neurochirurgie (DGNC) im Rahmen der Neurowoche 2010. Mannheim, 21.-25.09.2010. Dsseldorf: German Medical Science GMS Publishing House; 2010. DocP1716

DOI: 10.3205/10dgnc187, URN: urn:nbn:de:0183-10dgnc1874

Published: September 16, 2010

© 2010 Kogias et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.


Outline

Text

Objective: Resistance to temozolomide, the standard chemotherapy for gliomas in humans, represents an important issue in current therapy schemes. Emerging evidence suggests that nitric oxide may potentially lead to a sensitization of tumor cells to a variety of chemotherapeutic compounds. The nitric oxide donor PABA/NO selectively releases nitric oxide in GST-pi overexpressing glioma cells after enzymatic activation. We tested the hypothesis that PABA/NO may enhance the growth-inhibitory effect of temozolomide in U87 cells in vitro.

Methods: We exposed U87 cells to temozolomide concentrations between 1 然 and 100 然 alone as well as concomitantly with PABA/NO concentrations between 5 然 and 50 然 for 24 h. Viability was assessed after 24 h incubation, as well as 48 h and 72 h after drug removal by MTT assay. Statistical analysis was performed by ANOVA.

Results: The IC50 concentrations for PABA/NO and temozolomide alone were 45 然 and 100 然, respectively. PABA/NO significantly enhanced the growth-inhibitory effect of temozolomide in U87 glioma cells (p<0.0001). PABA/NO concentrations between 5 and 25 然 which did not have an intrinsic antiproliferative effect alone, lead to a significant increase in temozolomide cytotoxicity. Concomitant treatment of U87 cells with PABA/NO and temozolomide concentrations as low as 1 然 reduced cell viability up to 80%.

Conclusions: The nitric oxide donor PABA/NO significantly enhances the cytotoxic effect of temozolomide in U87 glioma cells in vitro. Using a nitric oxide donor to overcome resistance to temozolomide might be a new strategy to improve the efficacy of multimodal glioma treatment.