gms | German Medical Science

61st Annual Meeting of the German Society of Neurosurgery (DGNC) as part of the Neurowoche 2010
Joint Meeting with the Brazilian Society of Neurosurgery on the 20 September 2010

German Society of Neurosurgery (DGNC)

21 - 25 September 2010, Mannheim

Cytotoxic effects of statins and thiazolidinediones on meningioma cells

Meeting Abstract

  • Sonja Gehring - Neurochirurgische Klinik, Otto-von-Guericke Universität Magdeburg, Germany
  • Jorge Humberto Tapia-Pérez - Neurochirurgische Klinik, Otto-von-Guericke Universität Magdeburg, Germany
  • Elmar Kirches - Institut für Neuropathologie, Otto-von-Guericke Universität Magdeburg, Germany
  • Raimund Firsching - Neurochirurgische Klinik, Otto-von-Guericke Universität Magdeburg, Germany
  • Gerburg Keilhoff - Institut für Biochemie and Zellbiologie, Otto-von-Guericke Universität Magdeburg, Germany
  • Thomas Schneider - Neurochirurgische Klinik, Otto-von-Guericke Universität Magdeburg, Germany
  • Christian Mawrin - Institut für Neuropathologie, Otto-von-Guericke Universität Magdeburg, Germany

Deutsche Gesellschaft für Neurochirurgie. 61. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC) im Rahmen der Neurowoche 2010. Mannheim, 21.-25.09.2010. Düsseldorf: German Medical Science GMS Publishing House; 2010. DocP1736

DOI: 10.3205/10dgnc207, URN: urn:nbn:de:0183-10dgnc2079

Published: September 16, 2010

© 2010 Gehring 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: Statins are inhibitors of the cholesterol pathway with pleiotropic effects, while thiazolidinediones (TDZ) are peroxisomal proliferator activator receptor gamma (PPAR-gamma) agonists with potent pro-apoptotic activity. For both kinds of drugs, a cytotoxic effect against several human tumours is presumed. A direct comparison of several statins and TDZ has not been performed on meningioma cells until now.

Methods: We compared the cytotoxic effect of atorvastatin, lovastatin, pravastatin, lovastatin, and simvastatin and two TDZ, rosiglitazone and pioglitazone so as their combinations on various human meningioma cell lines using MTT-assay, cell cycle analysis and caspase-3 activity. Fibroblasts and astrocytes were used as controls.

Results: Simvastatin (SMV) and its combination with the TDZ pioglitazone (PGZ) turned out to be the most effective drugs. After 96 hours the half maximal inhibitory concentration of SMV in MTT-assays for benign and malignant meningioma cells was below 1uM. The addition of PGZ 10–40 uM further decreased the fraction of surviving cells. Cell cycle analysis suggested the induction of a cytotoxic rather than anti-proliferative effect. A strong caspase-3 induction suggested the activation of intrinsic apoptosis. Both drugs showed only a slight to moderate toxic effect on fibroblasts and astrocytes.

Conclusions: SMV showed a significant cytotoxic effect against human meningioma cells. The effect was modestly enhanced by PGZ. This allowed reduction in the dosage of SMV, leading to a remarkable cytotoxicity with clinically achievable and tolerated concentrations. In vivo studies are required.