Article
Cytotoxic effects of statins and thiazolidinediones on meningioma cells
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Published: | September 16, 2010 |
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Outline
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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.