PGC-1α induces apoptosis in human epithelial ovarian cancer cells through a PPARγ-dependent pathway

Peroxisome proliferator-activated receptor gamma (PPAR gamma) coactivator-1 alpha (PGC-1 alpha) coactivates multiple transcription factors and regulates several metabolic processes. The current study investigated the role of PGC-1 alpha in the induction of apoptosis in human epithelial ovarian cancer cells. The PGC-1 alpha mRNA level between human ovaries and human ovarian epithelial tumors was examined. by quantitative RT-PCR. Less PGC-1 alpha expression was found in the surface epithelium of malignant tumors compared with normal ovaries. Overexpression of PGC-1 alpha 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-1 alpha 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-1 alpha-induced apoptosis was partially, but not completely, blocked by PPAR gamma antagonist (GW9662), and suppression of PPAR gamma expression by siRNA also inhibited PGC-1 alpha-induced apoptosis in Ho-8910 cells. These data suggested that PGC-1 alpha exerted its effect through a PPAR gamma-dependent pathway. Our findings indicated that PGC-1 alpha was involved in the apoptotic signal transduction pathways and downregulation of PGC-1 alpha may be a key point in promoting epithelial ovarian cancer growth and progression.