Mechanism of the tumor suppressive effect of MnSOD overexpression.
The mitochondrial antioxidant protein manganese-containing superoxide dismutase (MnSOD) has been shown to be a new type of tumor suppressor protein. Overexpression of MnSOD protein inhibits growth in a wide variety of cancer types. This review examines the molecular mechanism of the tumor suppressive effect of MnSOD. Three species have been proposed to cause the tumor suppressive effect: superoxide radical, hydrogen peroxide and nitric oxide. At the present time, the evidence appears strongest that hydrogen peroxide is the effector molecule since both catalase and glutathione peroxidase has been shown to modulate the effect. Surprisingly, in different cancer cell lines, overexpression of GPx has been found to both decrease and increase the growth inhibitory effect of MnSOD overexpression. Knowledge of which molecule causes the tumor suppressive effect of MnSOD and the mechanism of action will likely lead to new therapies for the treatment of cancer.
Oberley
Larry W
LW
Free Radical and Radiation Biology, Department of Radiation Oncology, B180 Medical Laboratories, The University of Iowa City, Iowa 52242, USA. larry-oberley@uiowa.edu
D000818:Animals; D002374:Catalase / Q000378:metabolism*; D016166:Free Radical Scavengers / Q000378:metabolism* / Q000627:therapeutic use; D005979:Glutathione Peroxidase / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D013482:Superoxide Dismutase / Q000378:metabolism / Q000502:physiology / Q000627:therapeutic use; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000502:physiology / Q000627:therapeutic use
D016166:Free Radical Scavengers; D025521:Tumor Suppressor Proteins; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase