PGC-1α activates SIRT3 to modulate cell proliferation and glycolytic metabolism in breast cancer

Breast cancer is the leading cause of death among women. PGC-1 alpha plays an important role in the regulation of metabolic reprogramming in cancer cells. SIRT3 has significant implications for tumor growth. In this study, we explored the roles of PGC-1 alpha and SIRT3 in cell proliferation and mitochondrial energy metabolism alterations in breast cancer cells. The expression patterns of PGC-1 alpha and SIRT3 were examined using qRT-PCR and western blotting analysis. MCF-7 and MDA-MB-231 cells were infected with adenovirus to overexpress or knock down the expression of PGC-1 alpha and SIRT3. Cell viability and apoptosis were analyzed by CCK-8 and flow cytometry, respectively. Hexokinase 2, pyruvate kinase activities, as well as NAD(+)/NADH ratio and ATP concentration, were assessed by commercial kits. Glucose consumption was measured using the glucose oxidase method and lactic acid concentration was detected by lactate dehydrogenase kit. Expression levels of PGC-1 and SIRT3 were much lower in breast cancer patients, compared with the normal controls. Overexpression of PGC-1 alpha or SIRT3 both significantly promoted the apoptosis and inhibited the proliferation in MCF-7 and MDA-MB-231 cells. Additionally, PGC-1 alpha or SIRT3 also induced the inhibition of glycolysis metabolism. Moreover, the expression of SIRT3 was positively regulated by PGC-1 alpha. Silencing SIRT3 partly reversed the negative effects of PGC-1 alpha on glycolytic metabolism. These findings demonstrated that PGC-1 alpha/SIRT3 regulated cell proliferation and apoptosis of breast cancer through altering glycolysis, which may provide novel therapeutic strategies for breast cancer.

Automated summary

In this study, lower expression levels of PGC-1 alpha and SIRT3 were observed in breast cancer patients. Overexpression of PGC-1 alpha or SIRT3 significantly promoted apoptosis and inhibited proliferation in breast cancer cells. Furthermore, both PGC-1 alpha and SIRT3 were found to induce inhibition of glycolysis metabolism, with SIRT3 expression positively regulated by PGC-1 alpha.