gms | German Medical Science

58. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

26. bis 29.04.2007, Leipzig

JS-K, a glutathione S-transferase-activated nitric oxide donor, enhances imatinib (Glivec) cytotoxicity in malignant gliomas in vitro

JS-K, ein Glutathion S-Transferase aktivierter Stickstoffmonoxiddonor, verstärkt den zytotoxischen Effekt von Imatinib (Glivec) in malignen Gliomen in-vitro

Meeting Abstract

Suche in Medline nach

  • corresponding author A. Weyerbrock - Abteilung Allgemeine Neurochirurgie, Universitätsklinik Freiburg
  • B. Baumer - Abteilung Allgemeine Neurochirurgie, Universitätsklinik Freiburg
  • A. Papazoglou - Abteilung Stereotaktische Neurochirurgie, Universitätsklinik Freiburg

Deutsche Gesellschaft für Neurochirurgie. 58. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC). Leipzig, 26.-29.04.2007. Düsseldorf: German Medical Science GMS Publishing House; 2007. DocFR.09.08

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Veröffentlicht: 11. April 2007

© 2007 Weyerbrock et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen ( Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.



Objective: One component of chemoresistance is the overexpression of glutathione S-transferases (GSTs) in tumors. The diazeniumdiolate prodrug JS-K was designed to generate NO on enzymatic activation by GST targeting the NO effect selectively to GST-overexpressing tumors. There is some evidence that JS-K can reverse chemoresistance. The objective of this study was to evaluate potential synergistic effects of the tyrosine kinase inhibitor imatinib (Glivec) and JS-K in U87 glioma cells in vitro.

Methods: Human U87 cells were cultured in a standardized manner and then incubated with Glivec with doses between 1 and 50 µM for 24h. The dose-response curve for JS-K had been previously established with an IC50 of 25 and 20 µM for a 48 and 72 hour exposure, respectively. U87 cells were then incubated with 30 µM Glivec and 20 µM JS-K for 24 hours. Cell viability was assessed by MTT assay after 24, 48 and 72 hours. All experiments were repeated 4 times and done in triplicates. The data was analysed using ANOVA and Student's Newman Keul test.

Results: Glivec was significantly cytotoxic at 50 µM after 48 hours (p=0.03) and ≥20 µM after 72 hours (p=0.05). Concomittant exposure of U87 cells with Glivec and JS-K lead to a profound chemosensitization after 48 and 72 hours (p<0.001). While JS-K alone lead to a 50% reduction in cell viability, coexposure with Glivec resulted in 90% cell death after 48 hours. No significant recovery could be observed even after removal of both compounds.

Conclusions: This study shows for the first time that the diazeniumdiolate prodrug JS-K is effective in increasing imatinib (Glivec) cytotoxicity and also has potent intrinsic antiproliferative effects in GST-overexpressing U87 gliomas in vitro. JS-K might be a promising candidate for development of a new class of adjuvant prodrugs for cancer chemotherapy, particularly in drug-resistant tumors.