gms | German Medical Science

56. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)
3èmes journées françaises de Neurochirurgie (SFNC)

Deutsche Gesellschaft für Neurochirurgie e. V.
Société Française de Neurochirurgie

07. bis 11.05.2005, Strasbourg

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Experimental therapy of malignant gliomas using MS-275 in vitro and ex vivo

Experimentelle Therapie von malignen Gliomen mit MS-275 in-vitro und ex-vivo

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  • corresponding author I. Y. Eyüpoglu - Department of Neurosurgery, University of Erlangen-Nuremberg
  • E. Hahnen - Institute of Human Genetics, University of Cologne
  • C. Tränkle - Department of Pharmacology and Toxicology, Institute of Pharmacy, University of Bonn
  • I. Blümcke - Department of Neuropathology, University of Erlangen-Nuremberg
  • R. Fahlbusch - Department of Neurosurgery, University of Erlangen-Nuremberg

Deutsche Gesellschaft für Neurochirurgie. Société Française de Neurochirurgie. 56. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 3èmes journées françaises de Neurochirurgie (SFNC). Strasbourg, 07.-11.05.2005. Düsseldorf, Köln: German Medical Science; 2005. DocP158

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dgnc2005/05dgnc0426.shtml

Published: May 4, 2005

© 2005 Eyüpoglu 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

Inhibitors of histone deacetylases, in particular the benzamide MS-275, are promising novel compounds for the treatment of cancer, but have not been explored in brain tumors. Here, we describe MS-275 as a potent drug for experimental therapy of malignant gliomas.

Methods

Four malignant glioma cell lines (human U87 MG, rat C6, rat F98, mouse SMA-560) were analyzed in monolayer MTT cell growth and BrdU proliferation assays as well as fluorescent assisted cell sorting. The passage of the blood-brain-barrier was confirmed by i.p. injections of MS-275 in C57/b6 mice. Ex vivo cell growth was monitored using the organotypic glioma invasion model.

Results

Treatment of four malignant glioma cell lines with MS-275 significantly reduced cell growth in a concentration-dependent manner. Moreover, MS-275 altered the morphological phenotype of F98 glioma cells after 48 hours and induced G0/1 cell cycle arrest in a low micromolar range. Implantation of eGFP transfected F98 glioma cells into slice cultures of rat brain confirmed the cytostatic effect of MS-275, without neurotoxic side effects to the organotypic neuronal environment. In our model, the chemotherapeutic efficacy of MS-275 was comparable to that of the DNA alkylating drug temozolomide, whose beneficial impact on recurrent gliomas has recently been shown. Moreover, a combination of both compounds ex vivo increased the anti-glioma properties of MS-275.

Conclusions

Inhibitors of histone deacetylases, in particular MS-275, may thus be considered as promising compounds in the treatment of malignant gliomas.