Anticancer therapy by overexpression of superoxide dismutase.
Cancer cells are in general low in the enzymatic activities of both manganese-containing (MnSOD) and copper- and zinc-containing superoxide dismutase. We have hypothesized that part of the tumor cell phenotype is due to this loss of enzymatic activity. To test this hypothesis, we have overexpressed MnSOD via plasmid and adenovirus transfection in various cancer cell types and have shown tumor suppression. This tumor suppression is via a noncytotoxic mechanism and probably occurs due to cell-cycle perturbations. We have also shown that MnSOD overexpression causes the anticancer drug 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) to have increased cytotoxicity. Our hypothesis for the mechanism of action of this combination is that overexpression of MnSOD leads to increased peroxide levels and that BCNU inhibits peroxide removal. We currently are investigating the use of adenovirus MnSOD plus BCNU in the treatment of cancer. Results thus far are consistent with the idea that we can use the alterations in antioxidant enzymes observed in cancer cells to therapeutic advantage.
Oberley
L W
LW
Department of Radiology, University of Iowa, Iowa City 52242, USA. larry-oberley@uiowa.edu
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000975:Antioxidants / Q000378:metabolism; D002330:Carmustine / Q000627:therapeutic use; D006224:Cricetinae; D015316:Genetic Therapy; D005822:Genetic Vectors; D005979:Glutathione Peroxidase / Q000235:genetics / Q000502:physiology; D006801:Humans; D009062:Mouth Neoplasms / Q000628:therapy; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000628:therapy*; D011110:Polymorphism, Genetic; D051381:Rats; D013482:Superoxide Dismutase / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology; D000094765:Glutathione Peroxidase GPX1
D000970:Antineoplastic Agents; D000975:Antioxidants; D025521:Tumor Suppressor Proteins; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D002330:Carmustine; D000094765:Glutathione Peroxidase GPX1