Abstract
The mitochondrial antioxidant protein manganese superoxide dismutase (MnSOD) may represent a new type of tumor suppressor protein. Overexpression of the cDNA of this gene by plasmid or recombinant lentiviral transfection in various types of cancer leads to growth suppression both in vitro and in vivo. We previously determined that changes in MnSOD expression had bidirectional effects on adriamycin (ADR) when combined with nitric oxide (NO). Radiation induces free radicals in a manner similar to ADR, so we speculated that MnSOD combined with NO would also have a bidirectional effect on cellular radiosensitivity. To examine this hypothesis, TE-1 human esophageal squamous carcinoma cells were stably transfected using lipofectamine with a pLenti6-DEST plasmid containing human MnSOD cDNA at moderate to high overexpression levels or with no MnSOD insert. Blastidicin-resistant colonies were isolated, grown, and maintained in culture. We found that moderate overexpression of MnSOD decreased growth rates, plating efficiency, and increased apoptosis. However, high overexpression increased growth rates, plating efficiency, and decreased apoptosis. When combined with NO, moderate overexpression of MnSOD increased the radiosensitivity of esophageal cancer cells, whereas high MnSOD overexpression had the opposite effect. This finding suggests a potential new method to kill certain radioresistant tumors and to provide radioresistance to normal cells.
Highlights
Manganese superoxide dismutase (MnSOD) is a newly recognized anti-oncogene with low expression or detection in breast cancer (Soini et al, 2001), prostatic cancer (Wang et al, 2006), lung cancer (Zejnilovic et al, 2009), and esophageal cancer (Sun et al, 2011)
Using radiation and nitric oxide (NO), we evaluated whether the expression levels of manganese superoxide dismutase (MnSOD) may affect the biological behavior of esophageal cancer cells, and elucidate the mechanism of action using an reactive oxygen species (ROS) assay
MnSOD overexpression produced radioresistance when the plasmid containing MnSOD gene was transfected into caner cells, which was reversed by the transfection of antisense MnSOD cDNA (Epperly et al, 2003)
Summary
Manganese superoxide dismutase (MnSOD) is a newly recognized anti-oncogene with low expression or detection in breast cancer (Soini et al, 2001), prostatic cancer (Wang et al, 2006), lung cancer (Zejnilovic et al, 2009), and esophageal cancer (Sun et al, 2011). M-LeMnSOD cells demonstrated slower in vitro growth were seeded at 5000 cells/well in 96-well plates for 24 h and exposed to 1 mmol/L SNP following treatment with a 2-Gy dose of radiation after 12 h, and cultured for 48 h compared to the two untransfected MnSOD cell lines at 24, 48, and 72 h. There was a large increase in the relative survival fraction of H-LeMnSOD transfected cells compared to the two untransfected MnSOD cell lines.
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