Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04179 (MnSOD)
 2,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Anticancer therapy by overexpression of superoxide dismutase. 1149 57

Superoxide dismutases (SODs) have been found to decrease tumor formation and angiogenesis. SOD gene therapy, as with many other gene transfer strategies, may not completely inhibit tumor growth on its own. Thus, concomitant therapies are necessary to completely control the spread of this disease. We hypothesized that intratumoral injection of AdSOD in combination with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) chemotherapy would synergistically inhibit breast cancer growth. Our data indicate that BCNU when combined with SOD overexpression increased oxidative stress as suggested by elevated glutathione disulfide (GSSG) production in one of three breast cancer cell lines tested, at least in part due to glutathione reductase (GR) inactivation. The increased oxidative stress caused by BCNU combined with adenovirally expressed SODs, manganese or copper zinc SOD, decreased growth and survival in the three cell lines tested in vitro, but had the largest effect in the MDA-MB231 cell line, which showed the largest amount of oxidative stress. Delivery of MnSOD and BCNU intratumorally completely inhibited MDA-MB231 xenograft growth and increased nude mouse survival in vivo. Intravenous (iv) BCNU, recapitulating clinical usage, and intratumoral AdMnSOD delivery, to provide tumor specificity, provided similar decreased growth and survival in our nude mouse model. This cancer therapy produced impressive results, suggesting the potential use of oxidative stress-induced growth inhibitory treatments for breast cancer patients.
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PMID:Increased oxidative stress created by adenoviral MnSOD or CuZnSOD plus BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea) inhibits breast cancer cell growth. 1815 73