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

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

Meeting Abstract

  • 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

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2005/05dgnc0426.shtml

Veröffentlicht: 4. Mai 2005

© 2005 Eyüpoglu et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

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.