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

Abstract

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

Knockdown of peroxisome proliferator-activated receptor gamma coactivator-1 alpha increased apoptosis of human endometrial cancer HEC-1A cells

“…This phenomenon is known as the Warburg effect, and it is probably attributable to the damaged mitochondrial function within the cancer cells. Several studies have speculated that PGC-1α expression is lower in some cancer tissues, reducing the generation of mitochondria and increasing glycolysis, which are consistent with the Warburg effect 5–7. However, in recent years, studies have indicated that mitochondrial function is required for transformation and tumor growth 16–18.…”

“…In recent years, studies have shown that PGC-1α is involved in the development of some malignant tumors. Its expression is lower in some cancers than in normal tissues, including colon, breast, and ovarian cancer 5–7. However, its expression in other cancers is higher than in normal tissues.…”

“…It plays an important role in maintaining the balance between sugar, fat, and energy in the body; in the regulation of mitochondrial biosynthesis; and in other biological processes 2–4. In recent years, several studies have shown that the low PGC-1α expression is probably involved in malignant progression in a wide variety of tumor tissues, including breast cancer, colon cancer, and ovarian cancer 5–7. However, the study by Cormio et al and our previous study have shown that the expression of PGC-1α is elevated in endometrial carcinoma, and our preliminary study found that its expression is closely related to the clinical stage, depth of muscular infiltration, and lymph-node metastasis of the cancer 8,9…”

Smad4 mediates malignant behaviors of human ovarian carcinoma cell through the effect on expressions of E-cadherin, plasminogen activator inhibitor-1 and VEGF

“…It is an aggressive and fatal disease with a mortality rate of ∼50%. Ovarian carcinoma is expected to develop in 1 out of 70 women in their life times, over one woman out of 100 will ultimately succumb to complications associated with this disease (1)(2)(3). It is scarcely detected until its recurrence in the advanced stages.…”

“…It is scarcely detected until its recurrence in the advanced stages. The pathogenesis and malignance of ovarian cancer at molecular level are still poorly understood (1,2,4,5).…”