FOXO3a then transcriptionally activates MnSOD and catalase.10 These two antioxidant enzymes remove cellular ROS in normal cells; however, ROS levels remain high in cancer cells.9 Metformin has been reported to reduce cellular ROS levels in normal cell including mouse embryonic fibroblast cells and immune cells.15 However, metformin has been controversially reported to reduce16 or to increase17 cellular ROS level in cancer cells. This evidence concerns the gene SOD2 and cancer.