DOI QR코드

DOI QR Code

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

  • Sun, Guo-Gui (Department of Chemoradiotherapy, Tangshan People's Hospital) ;
  • Hu, Wan-Ning (Department of Chemoradiotherapy, Tangshan People's Hospital) ;
  • Wang, Ya-Di (Department of Radiotherapy, The Military General Hospital of Beijing PLA) ;
  • Yang, Cong-Rong (Department of Radiotherapy, The Fourth Hospital of Hebei Medical University) ;
  • Lu, Yi-Fang (Department of Endocrinology, Tangshan Workers Hospital)
  • Published : 2012.07.31

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.

References

  1. Biaglow JE, Mitchell J, Held K (1992). The importance of peroxide and superoxide in the X-ray response. Int J Radiat Oncol Biol Phys, 22, 665-9. https://doi.org/10.1016/0360-3016(92)90499-8
  2. Borrelli A, Schiattarella A, Mancini R (2009). A recombinant MnSOD is radioprotective for normal cells and radiosensitizing for tumor cells. Free Radic Biol Med, 46, 110-6. https://doi.org/10.1016/j.freeradbiomed.2008.10.030
  3. Bradford MM (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical Biochemistry, 72, 248-54. https://doi.org/10.1016/0003-2697(76)90527-3
  4. Church SL, Grant JW, Ridnour LA (1993). Increased manganese superoxide dismutase expression suppresses the malignant phenotype of human melanoma cells. Proc Natl Acad Sci USA, 90, 3113-7. https://doi.org/10.1073/pnas.90.7.3113
  5. Enzinger PC, Mayer RJ (2003). Esophageal cancer. N Engl J Med, 349, 2241-52. https://doi.org/10.1056/NEJMra035010
  6. Epperly MW, Gretton JE, Sikora CA (2003). Mitochondrial localization of superoxide dismutase is required for decreasing radiation-induced cellular damage. Radiat Res, 160, 568-78. https://doi.org/10.1667/RR3081
  7. Janssens MY, Verovski VN, Van den Berge DL, et al (1999). Radiosensitization of hypoxic tumour cells by S-nitroso-N-acetylpenicillamine implicates a bioreductive mechanism of nitric oxide generation. Br J Cancer, 79, 1085-9. https://doi.org/10.1038/sj.bjc.6690173
  8. Komatsu M, Kuroda M, Wang Y (2005). Manganese superoxide dismutase overexpression changes plating efficiency bidirectionally according to change in redox for SaOS2 human osteosarcoma cell line. Int J Oncol, 26, 853-62.
  9. Lau AT, Chiu JF (2006). Proteomic and biochemical analyses of in vitro carcinogen-induced lung cell transformation: synergism between arsenic and benzo[a] pyrene. Proteomics, 6, 1619-30. https://doi.org/10.1002/pmic.200500332
  10. Lau AT, He QY, Chiu JF (2004). A proteome analysis of the arsenite response in cultured lung cells: evidence for in vitro oxidative stress-induced apoptosis. Biochem J, 382, 641-50. https://doi.org/10.1042/BJ20040224
  11. Lau AT, Wang Y, Chiu JF (2008). Reactive oxygen species: current knowledge and applications in cancer research and therapeutic. J Cell Biochem, 104, 657-67. https://doi.org/10.1002/jcb.21655
  12. Lindsell CJ, Griffin MJ (1999). Thermal thresholds, vibrotactile thresholds and finger systolic blood pressures in dockyard workers exposed to hand-transmitted vibration. Int Arch Occup Environ Health, 72, 377-86. https://doi.org/10.1007/s004200050389
  13. Lin W, Song JD, Lin JY (2001). Nitric oxide effect of proliferation of stomach cancer cell line BGC-823. Chin J Cancer, 20, 1043-8.
  14. Li Z, Shi K, Guan L, (2010). ROS leads to MnSOD upregulation through ERK2 translocation and p53 activation in selenite-induced apoptosis of NB4 cells. FEBS Lett, 584, 2291-7. https://doi.org/10.1016/j.febslet.2010.03.040
  15. Nathan C (1992). Nitric oxide as a secretory product of mammalian cells. FASEB J, 6, 3051-64.
  16. Nishihira T, Kasai M, Mori S (1979). Characteristics of two cell lines (TE-1 and TE-2) derived from human squamous cell carcinoma of the esophagus. Gann, 70, 575-84.
  17. Niu Y, Wang H, Wiktor-Brown D (2010). Irradiated esophageal cells are protected from radiation-induced recombination by MnSOD gene therapy. Radiat Res, 173, 453-61. https://doi.org/10.1667/RR1763.1
  18. Orrenius S, Gogvadze V, Zhivotovsky B (2007). Mitochondrial oxidative stress: implications for cell death. Annu Rev Pharmacol Toxicol, 47, 143-83. https://doi.org/10.1146/annurev.pharmtox.47.120505.105122
  19. Ott M, Gogvadze V, Orrenius S, Zhivotovsky B (2007). Mitochondria, oxidative stress and cell death. Apoptosis, 12, 913-22. https://doi.org/10.1007/s10495-007-0756-2
  20. Ough M, Lewis A, Zhang Y (2004). Inhibition of cell growth by overexpression of manganese superoxide dismutase (MnSOD) in human pancreatic carcinoma. Free Radic Res, 38, 1223-33. https://doi.org/10.1080/10715760400017376
  21. Pavord SR, Murphy PT, Mitchell VE (1996). POEMS syndrome and Waldenstrom's macroglobulinaemia. J Clin Pathol, 49, 181-2. https://doi.org/10.1136/jcp.49.2.181
  22. Qu Y, Zhang H, Zhao S, et al (2010). The effect on radioresistance of manganese superoxide dismutase in nasopharyngeal carcinoma. Oncol Rep, 23, 1005-11.
  23. Qu Y, Zhao S, Hong J, et al (2010). Radiosensitive gene therapy through imRNA expression for silencing manganese superoxide dismutase. J Cancer Res Clin Oncol, 136, 953-9. https://doi.org/10.1007/s00432-009-0739-5
  24. Ressel L, Poli A (2010). Simultaneous double labelling of routinely processed paraffin tissue sections using combined immunoperoxidase, immunofluorescence, and digital image editing. Res Vet Sci, 88, 122-6. https://doi.org/10.1016/j.rvsc.2009.07.003
  25. Sang JR, Cheng YC, Shao GB (2010). Effect of nitric oxide on the proliferation of AGC gastric cancer cells. Chin J Cancer, 29, 166-70.
  26. Soini Y, Vakkala M, Kahlos K, et al (2001). MnSOD expression is less frequent in tumour cells of invasive breast carcinomas than in in situ carcinomas or non-neoplastic breast epithelial cells. J Pathol, 195, 156-62. https://doi.org/10.1002/path.946
  27. Sun GG, Wang YD, Chen LQ, et al (2011). Novel cancer suppressor gene for esophageal cancer: manganese superoxide dismutase. Dis esophagus, 24, 346-53. https://doi.org/10.1111/j.1442-2050.2010.01149.x
  28. Urano M, Kuroda M, Reynolds R (1995). Expression of manganese superoxide dismutase reduces tumor control radiation dose: gene-radiotherapy. Cancer Res, 55, 2490-3.
  29. Wang MC, Guo MF, Zhao GQ (2006). Research on mRNA expression level of MnSOD gene in prostate cancer and benign prostatic hyperplasia tissue. Chin J Gerontology, 26, 164-5.
  30. Wang Y, Kuroda M, Gao XS, et al (2005). Hydrogen peroxide overload increases adriamycin-induced apoptosis of SaOS(2) FM, a manganese superoxide dismutase-overexpressing human osteosarcoma cell line. Int J Oncol, 26, 1291-300.
  31. Weiss L, Stern S, Reich S, et al (1993). Effect of recombinant human manganese superoxide dismutase on radiosensitivity of murine B cell leukemia (BCL1) cells. Leuk Lymphoma, 10, 477-81. https://doi.org/10.3109/10428199309148205
  32. Weydert CJ, Waugh TA, Ritchie JM (2006). Overexpression of manganese or copper-zinc superoxide dismutase inhibits breast cancer growth. Free Radic Biol Med, 41, 226-37. https://doi.org/10.1016/j.freeradbiomed.2006.03.015
  33. Wispe JR, Clark JC, Burhans MS, (1989). Synthesis and processing of the precursor for human mangano-superoxide dismutase. Biochim Biophys Acta, 994, 30-6. https://doi.org/10.1016/0167-4838(89)90058-7
  34. Yan T, Oberley LW, Zhong W, et al (1996). Manganese-containing superoxide dismutase overexpression causes phenotypic reversion in SV40-transformed human lung fibroblasts. Cancer Res, 56, 2864-71.
  35. Zejnilovic J, Akev N, Yilmaz H, et al (2009). Association between manganese superoxide dismutase polymorphism and risk of lung cancer. Cancer Genet Cytogenet, 189, 1-4. https://doi.org/10.1016/j.cancergencyto.2008.06.017
  36. Zhang X, Epperly MW, Kay MA (2008). Radioprotection in vitro and in vivo by minicircle plasmid carrying the human manganese superoxide dismutase transgene. Hum Gene Ther, 19, 820-6. https://doi.org/10.1089/hum.2007.141
  37. Zhang Y, Smith BJ, Oberley LW (2006). Enzymatic activity is necessary for the tumor-suppressive effects of MnSOD. Antioxid Redox Signal, 8, 1283-93. https://doi.org/10.1089/ars.2006.8.1283
  38. Zhang Y, Smith BJ, Oberley LW (2006). Enzymatic activity is necessary for the tumor-suppressive effects of MnSOD. Antioxid Redox Signal, 8, 1283-93. https://doi.org/10.1089/ars.2006.8.1283
  39. Zhong W, Oberley LW, Oberley TD, et al (1997). Suppression of the malignant phenotype of human glioma cells by overexpression of manganese superoxide dismutase. Oncogene, 14, 481-90. https://doi.org/10.1038/sj.onc.1200852

Cited by

  1. 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 vol.14, pp.3, 2013, https://doi.org/10.7314/APJCP.2013.14.3.1937
  2. Interactions between Filamin A and MMP-9 Regulate Proliferation and Invasion in Renal Cell Carcinoma vol.15, pp.8, 2014, https://doi.org/10.7314/APJCP.2014.15.8.3789
  3. Manganese Superoxide Dismutase (MnSOD Val-9Ala) Gene Polymorphism and Susceptibility to Gastric Cancer vol.16, pp.2, 2015, https://doi.org/10.7314/APJCP.2015.16.2.485