Pioglitazone Effect on Glioma Stem Cell Lines: Really a Promising Drug Therapy for Glioblastoma?

Glioblastoma multiforme (GBM) represents one of the most frequent malignant brain tumors. Current therapies do not provide real solutions to this pathology. Their failure can be ascribed to a cell subpopulation with stem-like properties called glioma stem cells (GSCs). Therefore, new therapeutic strategies GSC-targeted are needed. PPAR gamma, a nuclear receptor involved in lipid metabolism, has already been indicated as a promising target for antineoplastic therapies. Recent studies have reported that synthetic PPAR gamma. agonists, already in clinical use for the treatment of type II diabetes, exhibit antineoplastic effects in a wide range of malignant tumor cells, including glioma cells. We investigated the effect of the synthetic PPAR gamma agonist Pioglitazone on viability, proliferation, morphology, and differentiation in six GSC lines isolated from GBM patients. We also analyzed Pioglitazone-induced changes in transcriptional levels of Wnt/beta catenin related genes. Results showed that response to Pioglitazone was heterogeneous inducing an evident decrease of cell viability and proliferation only in a subset of GSC lines. We did not find any sign of cell differentiation neither observing cell morphology nor analyzing the expression of stemness and differentiation markers. Moreover, Wnt/beta signaling pathway was only mildly affected from a transcriptional point of view after Pioglitazone exposure.