Artikel
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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Autoren
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I. Y. Eyüpoglu
- Department of Neurosurgery, University of Erlangen-Nuremberg
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E. Hahnen
- Institute of Human Genetics, University of Cologne
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C. Tränkle
- Department of Pharmacology and Toxicology, Institute of Pharmacy, University of Bonn
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I. Blümcke
- Department of Neuropathology, University of Erlangen-Nuremberg
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R. Fahlbusch
- Department of Neurosurgery, University of Erlangen-Nuremberg
| Veröffentlicht: | 4. Mai 2005 |
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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.
