Cytotoxic effects of statins and thiazolidinediones on meningioma cells
Statins are inhibitors of the cholesterol synthesis pathway with pleiotropic effects, while thiazolidinediones (TDZ) are peroxisomal proliferator activator receptor Î³ (PPAR-Î³) agonists with potent proapoptotic activity. For both groups of substances a cytotoxic effect against several human tumors is presumed. Direct comparison of several statins and TDZ has not been performed on meningioma cells until now. We compared the antiproliferative/cytotoxic effect of five statins, two TDZ, and their combinations on various human meningioma cell lines and nontumorous cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, cell cycle analysis, and caspase-3 assay. Simvastatin (SMV) and its combination with the TDZ pioglitazone (PGZ) turned out to be the most effective treatment. After 96Â h the 50% inhibition concentration (IC50) of SMV in MTT assays for two more sensitive meningioma cell lines (one benign and one malignant) was below 0.9Â Î¼M, while the IC50 was 2.8Â Î¼M or higher for two other meningioma lines. Fluorescence-activated cell sorting (FACS) analysis suggested that MTT results mostly represented cytotoxic rather than antiproliferative effects. Strong caspase-3 induction suggested participation of intrinsic apoptosis in meningioma cell death. In contrast, SMV showed no substantial effects on fibroblasts and astrocytes. Addition of 40Â Î¼M PGZ significantly decreased the fraction of clonogenic cells in soft-agar assays, as compared with 2.8Â Î¼M SMV alone. Taken together, SMV showed a significant cytotoxic effect against human meningioma cells, which was moderately enhanced by PGZ.