Oxidative Stress Induced by MnSOD-p53 Interaction: Pro- or Anti-Tumorigenic?

Abstract

The formation of reactive oxygen species (ROS) is a result of incomplete reduction of molecular oxygen during cellular metabolism. Although ROS has been shown to act as signaling molecules, it is known that these reactive molecules can act as prooxidants causing damage to DNA, proteins, and lipids, which over time can lead to disease propagation and ultimately cell death. Thus, restoring the protective antioxidant capacity of the cell has become an important target in therapeutic intervention. In addition, a clearer understanding of the disease stage and molecular events that contribute to ROS generation during tumor promotion can lead to novel approaches to enhance target specificity in cancer progression. This paper will focus on not only the traditional routes of ROS generation, but also on new mechanisms via the tumor suppressor p53 and the interaction between p53 and MnSOD, the primary antioxidant enzyme in mitochondria. In addition, the potential consequences of the p53-MnSOD interaction have also been discussed. Lastly, we have highlighted clinical implications of targeting the p53-MnSOD interaction and discussed recent therapeutic mechanisms utilized to modulate both p53 and MnSOD as a method of tumor suppression.