Journal article
Overexpression of copper zinc superoxide dismutase suppresses human glioma cell growth
Cancer research (Chicago, Ill.), Vol.62(4), pp.1205-1212
2002
PMID: 11861405
Abstract
Copper zinc superoxide dismutase (CuZnSOD) is an essential primary antioxidant enzyme that converts superoxide radical to hydrogen peroxide and molecular oxygen in the cytoplasm. Cytosolic glutathione peroxidase (GPx) converts hydrogen peroxide into water. The overall goal of the present study was to explore the possible role of the antioxidant enzyme CuZnSOD in expression of the malignant phenotype. We hypothesized that overexpression of CuZnSOD would lead to the suppression of at least part of the human malignant phenotype. To test this hypothesis, human CuZnSOD cDNA was transfected into U118-9 human malignant glioma cells. CuZnSOD activity levels increased 1.5-, 2.0-, 2.6-, and 3.5-fold, respectively, in four table transfected cell lines compared with wild type and vector controls. Overexpression of CuZnSOD altered cellular antioxidant enzyme profiles, including those of manganese superoxide dismutase, catalase, and GPx. The transfected clone with the highest CuZnSOD:GPx ratio (3.5) showed a 42% inhibition of tumor cell growth in vitro. The decreased rate of tumor cell growth in vitro was strongly correlated with the enzyme activity ratio of CuZnSOD:GPx. Glioma cells that stably overexpressed CuZnSOD demonstrated additional suppressive effects on the malignant phenotype when compared with the parental cells and vector controls. These cells showed decreased plating efficiency, elongated cell population doubling time, lower clonogenic fraction in soft agar, and, more significantly, inhibition of tumor formation in nude mice. This work suggested that CuZnSOD is a new tumor suppressor gene. Increased intracellular ROS levels were found in cells with high activity ratios of CuZnSOD:GPx. Change in the cellular redox status, especially change attributable to the accumulation of hydrogen peroxide or other hydroperoxides, is a possible reason to explain the suppression of tumor growth observed in CuZnSOD-overexpressing cells.
Details
- Title: Subtitle
- Overexpression of copper zinc superoxide dismutase suppresses human glioma cell growth
- Creators
- Ying Zhang - Free Radical and Radiation Biology Program, Department of Radiation Oncology, B180 Medical Laboratories, College of Medicine, The University of Iowa, Iowa City, Iowa 52242, United StatesWeiling Zhao - Free Radical and Radiation Biology Program, Department of Radiation Oncology, B180 Medical Laboratories, College of Medicine, The University of Iowa, Iowa City, Iowa 52242, United StatesHannah J ZHANG - Free Radical and Radiation Biology Program, Department of Radiation Oncology, B180 Medical Laboratories, College of Medicine, The University of Iowa, Iowa City, Iowa 52242, United StatesFrederick E DOMANN - Free Radical and Radiation Biology Program, Department of Radiation Oncology, B180 Medical Laboratories, College of Medicine, The University of Iowa, Iowa City, Iowa 52242, United StatesLarry W OBERLEY - Free Radical and Radiation Biology Program, Department of Radiation Oncology, B180 Medical Laboratories, College of Medicine, The University of Iowa, Iowa City, Iowa 52242, United States
- Resource Type
- Journal article
- Publication Details
- Cancer research (Chicago, Ill.), Vol.62(4), pp.1205-1212
- Publisher
- American Association for Cancer Research; Philadelphia, PA
- PMID
- 11861405
- ISSN
- 0008-5472
- eISSN
- 1538-7445
- Language
- English
- Date published
- 2002
- Academic Unit
- Pathology; Surgery; Radiation Oncology
- Record Identifier
- 9984047982902771
Metrics
22 Record Views