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.
Zhang
Yan
Y
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.
Ba
Yi
Y
Liu
Chang
C
Sun
Guoxun
G
Ding
Li
L
Gao
Songyuan
S
Hao
Jihui
J
Yu
Zhentao
Z
Zhang
Junfeng
J
Zen
Ke
K
Tong
Zhongsheng
Z
Xiang
Yang
Y
Zhang
Chen-Yu
CY
D000328:Adult; D000368:Aged; D000813:Anilides / Q000494:pharmacology; D017209:Apoptosis; D045744:Cell Line, Tumor; D018284:Cystadenocarcinoma, Serous / Q000378:metabolism / Q000473:pathology*; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D006360:Heat-Shock Proteins / Q000502:physiology*; D006801:Humans; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D047495:PPAR gamma / Q000502:physiology*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D015398:Signal Transduction; D014157:Transcription Factors / Q000502:physiology*
C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D006360:Heat-Shock Proteins; D047495:PPAR gamma; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors