Mitochondrial MnSOD Expression in Ovarian Cancer: Role in Cell Proliferation and Response to Oxidative Stress

Superoxide dismutases (SOD) are important antioxidant enzymes responsible for the elimination of superoxide radical (O2). The manganese-containing SOD (MnSOD) has been suggested to have tumor suppressor function and is located in the mitochondria where the majority of O2 is generated during respiration. Although increased reactive oxygen species (ROS) in cancer cells has long been recognized, the expression of MnSOD in cancer and its role in cancer development remain elusive. The present study used human tissue microarray to analyze MnSOD expression in primary ovarian cancer tissues, benign ovarian lesions, and normal ovary epithelium. Significantly higher levels of MnSOD protein expression were detected in the malignant tissues compared to normal tissues (p<0.05). In experimental systems, suppression of MnSOD expression by siRNA caused a 70% increase of superoxide in ovarian cancer cells, leading to stimulation of cell proliferation in vitro and more aggressive tumor growth in vivo. Furthermore, stimulation of mitochondrial O2 production induced an increase of MnSOD expression. Our findings suggest that the increase in MnSOD expression in ovarian cancer is a cellular response to intrinsic ROS stress, and that scavenging of superoxide by SOD may alleviate the ROS stress and thus reduce the simulating effect of ROS on cell growth. INTRODUCTION