Chondrosarcoma and Peroxisome Proliferator-Activated Receptor

Induction of differentiation and apoptosis in cancer cells by ligands of PPARgamma is a novel therapeutic approach to malignant tumors. Chondrosarcoma (malignant cartilage tumor) and OUMS-27 cells (cell line established from grade III human chondrosarcoma) express PPARgamma. PPARgamma ligands inhibited cell proliferation in a dose-dependent manner, and induced apoptosis of OUMS-27. The higher-grade chondrosarcoma expressed a higher amount of antiapoptotic Bcl-xL in vivo. The treatment of OUMS-27 by 15d-PGJ(2), the most potent endogenous ligand for PPARgamma, downregulated expression of Bcl-xL and induced transient upregulation of proapoptotic Bax, which could accelerate cytochrome c release from mitochondria to the cytosol, followed by induction of caspase-dependent apoptosis. 15d-PGJ(2) induced the expression of CDK inhibitor p21 protein in human chondrosarcoma cells, which appears to be involved in the mechanism of inhibition of cell proliferation. These findings suggest that targeted therapy with PPARgamma ligands could be a novel strategy against chondrosarcoma.