Effect of PPAR gamma ligands on cell death of astrocytoma cells

Abstract

Purpose: The purpose of this study is to determine the molecular mechanism responsible for the anti-tumor effect of PPARg ligands. Materials and Methods: Apoptosis was measured by flow cytometric analysis and mitochondrial transmembrane potential was determined using an inverted epifluorescence microscope and FACS analysis after staining with JC-1 and TMRE. Intracellular levels of reactive oxygen species (ROS) were determined after staining with DCF-DA. Results: PPARg ligands (troglitazone, ciglitazone and 15d-PGJ2) induced apoptotic cell death of astrocytoma cells but not human primary cultured fetal astrocyte. PPARg ligands generated intracellular ROS within 1 h and subsequentlt induced depolarization of mitochondrial transmembrane and apoptosis. PPARg ligands-induced mitochondrial depolarization and apoptosis were suppressed by pretreatment with ROS scavengers, NAC and EGCG. These results collectively indicate that a PPARg ligands-induced apoptosis is mediated by generation of ROS and subsequent depolarization of mitochondrial transmembrane potential and caspase 3 activation. Conclusion: Our results suggest that PPARg ligands, antidiabetic drugs, might be utilized as an effective anti-cancer therapy for treatment of highly malignant astrocytoma.