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Anticancer therapy by overexpression of superoxide dismutase

L W Oberley1

  • 1Department of Radiology, University of Iowa, Iowa City 52242, USA. larry-oberley@uiowa.edu

Antioxidants & Redox Signaling
|August 9, 2001
PubMed

Insights

Overexpressing manganese superoxide dismutase (MnSOD) in cancer cells suppressed tumors and enhanced chemotherapy effectiveness. This approach targets altered antioxidant enzymes for cancer treatment advantage.

Area of Science:

  • Biochemistry
  • Oncology
  • Molecular Biology

Background:

  • Cancer cells exhibit reduced enzymatic activity in manganese-containing superoxide dismutase (MnSOD) and copper/zinc-containing superoxide dismutase.
  • This enzymatic deficiency is hypothesized to contribute to the tumor cell phenotype.

Purpose of the Study:

  • To investigate the therapeutic potential of restoring MnSOD activity in cancer cells.
  • To determine if MnSOD overexpression can suppress tumor growth and enhance the efficacy of chemotherapy.

Main Methods:

  • Overexpression of MnSOD in various cancer cell types using plasmid and adenovirus transfection.
  • Assessment of tumor suppression and cytotoxicity of combined MnSOD overexpression and BCNU treatment.

Main Results:

  • MnSOD overexpression demonstrated tumor suppression through a noncytotoxic mechanism, likely involving cell-cycle perturbations.
  • Combined MnSOD overexpression and BCNU treatment resulted in increased cytotoxicity, suggesting a synergistic effect.
  • Hypothesized mechanism involves elevated peroxide levels due to MnSOD overexpression, with BCNU inhibiting peroxide removal.

Conclusions:

  • Restoring MnSOD activity can be a viable strategy for cancer therapy.
  • Targeting altered antioxidant enzyme levels in cancer cells offers a therapeutic advantage.
  • Further investigation into adenovirus-mediated MnSOD and BCNU combination therapy is warranted.

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