gms | German Medical Science

60th Annual Meeting of the German Society of Neurosurgery (DGNC)
Joint Meeting with the Benelux countries and Bulgaria

German Society of Neurosurgery (DGNC)

24 - 27 May 2009, Münster

Article

Send article

Growth-inhibition and chemosensitization to imatinib and carboplatin by the nitric oxide-donor PABA/NO in U87 glioma cells in vitro

Meeting Abstract

Search Medline for

  • E. Kogias - Allgemeine Neurochirurgie, Universitätsklinikum Freiburg
  • A. Papazoglou - Stereotaktische Neurochirurgie, Universitätsklinikum Freiburg
  • B. Baumer - Allgemeine Neurochirurgie, Universitätsklinikum Freiburg
  • A. Weyerbrock - Allgemeine Neurochirurgie, Universitätsklinikum Freiburg

Deutsche Gesellschaft für Neurochirurgie. 60. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit den Benelux-Ländern und Bulgarien. Münster, 24.-27.05.2009. Düsseldorf: German Medical Science GMS Publishing House; 2009. DocP14-03

doi: 10.3205/09dgnc401, urn:nbn:de:0183-09dgnc4015

Published: May 20, 2009

© 2009 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: Nitric oxide has potent dose-dependent growth-inhibitory and chemosensitizing effects in tumors. The nitric oxide (NO)-donor PABA/NO (O2-(2,4-dinitro-5-(N-methyl-N-4-carboxyphenylamino) phenyl] 1-N,N-dimethylamino)diazen-1-ium-1,2-diolate) selectively releases NO after enzymatic activation by the glutathione S-transferase (GST-π) which is overexpressed in malignant glioma cells and contributes to chemoresistance.

Methods: We evaluated the growth-inhibitory effect of PABA/NO alone (2-100 µM) and in combination with imatinib (Glivec®, 10-30 µM) and carboplatin (25-500 µM) in U87 cells. Fibroblasts were tested as non-neoplastic controls. Viability was assessed by MTT assay after incubation for 24h, and 48 & 72h after drug removal. Statistical analysis was performed by ANOVA and post-hoc tests.

Results: PABA/NO had a dose-dependent cytotoxic effect in U87 cells with an IC50 of 45 µM (p<0.0001). Imatinib as monotherapy was not effective in U87 cells. However, concomitant incubation of U87 with doses of PABA/NO and imatinib which did not have a significant cytotoxic effect alone induced a significant increase in cell death indicating a chemosensitizing effect of PABA/NO (p<0.0001). A dose-dependent cytotoxic effect was observed after carboplatin exposure (IC50 150 µM) which could be increased in combination with PABA/NO doses ≥25 µM (p=0.008). Fibroblasts were significantly less affected by PABA/NO (p=0.0016) than U87 cells. GST-π expression was confirmed by immunocytochemistry.

Conclusions: PABA/NO has potent cytotoxic and chemosensitizing effects in U87 glioma cells. Current research activities focus on studying the intracellular pathways involved in the effect of the NO donor and on safety and efficacy in an intracranial U87 tumor model.