Antiapoptotic effects of mitochondrial manganese superoxide dismutase in ovarian cancer cells

Abstract

Objective: To investigate the protein expression levels of manganese superoxide dismutase (MnSOD) in ovarian cancer cell lines and ovarian surface epithelial (OSE) cells and the possible correlation between MnSOD expression and resistance to stress-induced apoptosis. Methods: Protein expression levels were measured by immunoblot analysis. Expression of MnSOD was manipulated by overexpression or small interfering RNA. Cell proliferation was examined by cell growth, colony formation, and MTT assays, whereas cell death was measured by DAPI and TUNEL assays. Results: MnSOD expression was significantly higher in most ovarian cancer cell lines than OSE. Overexpression of MnSOD in ovarian cancer cells conferred a strong decrease in cell proliferation and an increase of apoptosis, whereas targeted knockdown of endogenous MnSOD reduced apoptosis. Furthermore, stimulation of mitochondrial superoxide induced an increase of MnSOD expression, suggesting that MnSOD may alleviate the reactive oxygen species stress in these cells. We also showed that overexpression of MnSOD protected ovarian cancer cells against apoptosis induced by treatment of rotenone, hydrogen peroxide, or hypoxia-mimicking agents cobalt chloride and deferoxamine. Conclusion: Upregulation of MnSOD is one of the mechanisms which may increase resistance to oxidative stress and apoptosis in ovarian cancer cells.