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Experimental therapy of malignant gliomas using the inhibitor of histone deacetylase MS-275

Eyupoglu, I. Y., Hahnen, E., Tränkle, C., Savaskan, N. E., Siebzehnrubl, Florian ORCID: https://orcid.org/0000-0001-8411-8775, Buslei, R., Lemke, D., Wick, W., Fahlbusch, R. and Blümcke, I. 2006. Experimental therapy of malignant gliomas using the inhibitor of histone deacetylase MS-275. Molecular Cancer Therapeutics 5 (5) , p. 1248. 10.1158/1535-7163.MCT-05-0533

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Abstract

Inhibitors of histone deacetylases are promising compounds for the treatment of cancer but have not been systematically explored in malignant brain tumors. Here, we characterize the benzamide MS-275, a class I histone deacetylase inhibitor, as potent drug for experimental therapy of glioblastomas. Treatment of four glioma cell lines (U87MG, C6, F98, and SMA-560) with MS-275 significantly reduced cell growth in a concentration-dependent manner (IC90, 3.75 μmol/L). Its antiproliferative effect was corroborated using a bromodeoxyuridine proliferation assay and was mediated by G0-G1 cell cycle arrest (i.e., up-regulation of p21/WAF) and apoptotic cell death. Implantation of enhanced green fluorescent protein–transfected F98 glioma cells into slice cultures of rat brain confirmed the cytostatic effect of MS-275 without neurotoxic damage to the organotypic neuronal environment in a dose escalation up to 20 μmol/L. A single intratumoral injection of MS-275 7 days after orthotopic implantation of glioma cells in syngeneic rats confirmed the chemotherapeutic efficacy of MS-275 in vivo. Furthermore, its propensity to pass the blood-brain barrier and to increase the protein level of acetylated histone H3 in brain tissue identifies MS-275 as a promising candidate drug in the treatment of malignant gliomas.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
European Cancer Stem Cell Research Institute (ECSCRI)
Publisher: American Association for Cancer Research
ISSN: 1535-7163
Last Modified: 27 Oct 2022 08:49
URI: https://orca.cardiff.ac.uk/id/eprint/63482

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