gms | German Medical Science

62nd Annual Meeting of the German Society of Neurosurgery (DGNC)
Joint Meeting with the Polish Society of Neurosurgeons (PNCH)

German Society of Neurosurgery (DGNC)

7 - 11 May 2011, Hamburg

NO donor JS-K enhances cytotoxic effects of radiotherapy in U87 gliomas in vitro

Meeting Abstract

  • N.K. Thiede - Abteilung Allgemeine Neurochirurgie, Universitätsklinikum Freiburg
  • B. Baumer - Abteilung Allgemeine Neurochirurgie, Universitätsklinikum Freiburg
  • N. Osterberg - Abteilung Allgemeine Neurochirurgie, Universitätsklinikum Freiburg
  • S. Bette - Abteilung Allgemeine Neurochirurgie, Universitätsklinikum Freiburg
  • A. Weyerbrock - Abteilung Allgemeine Neurochirurgie, Universitätsklinikum Freiburg

Deutsche Gesellschaft für Neurochirurgie. Polnische Gesellschaft für Neurochirurgen. 62. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgen (PNCH). Hamburg, 07.-11.05.2011. Düsseldorf: German Medical Science GMS Publishing House; 2011. DocP 083

doi: 10.3205/11dgnc304, urn:nbn:de:0183-11dgnc3040

Published: April 28, 2011

© 2011 Thiede et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Objective: The dismal prognosis of glioblastoma patients is largely caused by a high level of drug and radioresistance. The nitric oxide donor JS-K releases nitric oxide in GST-overexpressing tumor cells after enzymatic activation by glutathione-S-transferase (GST) resulting in growth inhibition, chemosensitization and anti-migration. The objective of this work was to analyze potential radiosensitizing effects of JS-K in U87 glioma cells in vitro.

Methods: U87 cells were exposed to increasing JS-K-concentrations (5–50 µM) for 4 h and were irradiated with 2, 5 or 10 Gray (Gy) 2h after JS-K-application. Cell viability and proliferative activity were assessed by MTT and colony formation assays at the end of treatment and in 48 h intervals up to 216 h. The induction of DNA-damage was analyzed by immunocytochemical staining of H2AX-Foci directly and 24 h after treatment. The influence of JS-K on cell cycle distribution and arrest was assessed by FACS analysis. All experiments were done in triplicates and repeated three times. Statistical analysis was either performed by Jonckheere-Terpstra-Test or by student’s T-Test.

Results: U87 were highly radioresistant and showed only a small dose- and time dependent reduction of cell viability up to 216 h after exposure. JS-K showed a strong dose-dependent antiproliferative effect with an IC50 of for 15 µM. Colony formation was abolished after JS-K treatment. Concomitant treatment with JS-K significantly enhanced the efficacy of irradiation with 2 Gy as late as 216h after treatment. Cell death was the result of JS-K-induced enhanced DNA-damage and decreased repair of DNA-double-strand-breaks. JS-K caused incorrect G1-arrest and a reentry of incompletely repaired U87-cells at an early stage.

Conclusions: JS-K sensitizes U87 glioma cell to irradiation and has potent antiproliferative and DNA damaging effects. This warrants further investigation of NO-releasing compounds as radiosensitizers in multimodal glioblastoma therapy.