PGC-1alpha induces apoptosis in human epithelial ovarian cancer cells through a PPARgamma-dependent pathway.

Peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator-1 alpha (PGC-1alpha) coactivates multiple transcription factors and regulates several metabolic processes. The current study investigated the role of PGC-1alpha in the induction of apoptosis in human epithelial ovarian cancer cells. The PGC-1alpha mRNA level between human ovaries and human ovarian epithelial tumors was examined by quantitative RT-PCR. Less PGC-1alpha expression was found in the surface epithelium of malignant tumors compared with normal ovaries. Overexpression of PGC-1alpha in human epithelial ovarian cancer cell line Ho-8910 induced cell apoptosis through the coordinated regulation of Bcl-2 and Bax expression. Microarray analyses confirmed that PGC-1alpha dramatically affected the apoptosis-related genes in Ho-8910 cells. Mitochondrial functional assay showed that the induction of apoptosis was through the terminal stage by the release of cytochrome c. Furthermore, PGC-1alpha-induced apoptosis was partially, but not completely, blocked by PPARgamma antagonist (GW9662), and suppression of PPARgamma expression by siRNA also inhibited PGC-1alpha-induced apoptosis in Ho-8910 cells. These data suggested that PGC-1alpha exerted its effect through a PPARgamma-dependent pathway. Our findings indicated that PGC-1alpha was involved in the apoptotic signal transduction pathways and downregulation of PGC-1alpha may be a key point in promoting epithelial ovarian cancer growth and progression.