Mitochondrial manganese superoxide dismutase protects ovarian cancer cells from oxidative stress-induced apoptosis

The manganese superoxide dismutase (MnSOD), located in the mitochondria, is a major antioxidant enzyme that plays an important role in protecting cells from oxidative damage. MnSOD has been suggested to have tumor suppressor function in many cancer types. Surprisingly, the levels of MnSOD in ovarian carcinomas were found elevated compared with normal ovarian epithelium. In this study, we aimed to investigate the levels of MnSOD protein in ovarian cancer cell lines and ovarian surface epithelial (OSE) cells and a possible link between MnSOD expression and resistance to apoptosis. We showed that MnSOD protein was abundant in most ovarian cancer cell lines but was at very low levels in OSE. MnSOD overexpression in ovarian cancer cells caused a ~50% decrease of cell proliferation and an increase of apoptosis, whereas targeted inhibition of endogenous MnSOD using small interfering RNA promoted growth of these cells, confirming the effect was MnSOD specific. Furthermore, stimulation of mitochondrial superoxide (O2 - ) production induced an increase of MnSOD expression, suggesting that MnSOD may alleviate the reactive oxygen species stress in these cells. Our data also showed that MnSOD overexpression protected ovarian cancer cells from apoptosis induced by treatment with rotenone, hydrogen peroxide, or hypoxia-mimicking agents cobalt chloride and deferoxamine compared with the parental and neo control cell lines. Together, these data suggest upregulation of MnSOD in ovarian cancer cells is one of the mechanisms which may increase resistance to oxidative stress and apoptosis in cancer cells