Bidirectional Regulation of Manganese Superoxide Dismutase (MnSOD) on the Radiosensitivity of Esophageal Cancer Cells

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.

Radiation-induced SOD2 overexpression sensitizes colorectal cancer to radiation while protecting normal tissue

“…Previous studies also showed that overexpression of SOD2 in tumor cells can enhance radiosensitivity of tumor cells rather than act as a protector [12, 26, 27]. The relevant mechanism, which is unknown at present, may be the different redox state in tumor cells versus the normal cells [11, 26].…”

Different Association of Manganese Superoxide Dismutase Gene Polymorphisms with Risk of Prostate, Esophageal, and Lung Cancers: Evidence from a Meta-analysis of 20,025 Subjects

“…Studies on human tissue specimens showed that MnSOD was absent or reduced in breast cancer (Soini et al, 2001) and prostate cancer (Wang et al, 2006). Nevertheless, MnSOD overexpression to decrease ROS levels in the cells was able to reduce cell doubling time and plating efficiency of osteosarcoma cells, thus reducing its transfection rate Komatsu et al, 2005 ;Sun et al, 2012). MnSOD expression was also able to inhibit or reverse the malignant phenotype and growth of human fibroblast SV40 (Yan et al, 1996), malignant melanoma tumor (Zwacka et al, 1993), and glioma cells (Zhong et al, 2005).…”

Manganese Superoxide Dismutase (MnSOD Val-9Ala) Gene Polymorphism and Susceptibility to Gastric Cancer

“…MnSOD is the important antioxidant agent in the mitochonderia that catalyzes the dismutation of superoxide radicals to hydrogen peroxide form and detoxification of mitochondrial ROS (Sun et al, 2012). The MnSOD gene as tumor suppressor gene is located on chromosome 6 at q25.3.…”