Skip to main content

Advertisement

Log in

Effects of manganese superoxide dismutase (MnSOD) expression on regulation of esophageal cancer cell growth and apoptosis in vitro and in nude mice

  • Research Article
  • Published:
Tumor Biology

Abstract

Manganese superoxide dismutase (MnSOD) catalyzes superoxide radical (O2 ) into hydrogen peroxide (H2O2), which is further catalyzed by the combined action of glutathione peroxidase (GPx) and catalase (CAT) into water and oxygen. MnSOD plays a role in cell protection from superoxide damage. This study aimed to investigate the effects of MnSOD on regulation of esophageal squamous cell carcinoma cell growth, apoptosis, and cell cycle distribution in vitro and tumor formation and growth in nude mouse xenografts. The data showed that differential levels of MnSOD expression had different effects on tumor cell proliferation, apoptosis, plating efficiency (PE), and cell cycle distribution in vitro and tumor formation and growth in nude mice. In particular, high levels of MnSOD expression promoted TE-1 cell growth and PE rate in vitro and in nude mice, whereas moderate MnSOD expression suppressed tumor cell growth and PE rate but induced more cell apoptosis. Thus, these data demonstrated the dual effects of MnSOD protein in esophageal squamous cell carcinoma and further study will confirm these current data.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Schuchert MJ, Luketich JD, Landreneau RJ. Management of esophageal cancer. Curr Probl Surg. 2010;47:845–946.

    Article  PubMed  Google Scholar 

  2. Zhong WX, Oberley LW, Oberley TD, St Clair DK. Suppression of the malignant phenotype of human glioma cells by overexpression of manganese superoxide dismutase. Oncogene. 1997;14:481–90.

    Article  PubMed  CAS  Google Scholar 

  3. Oberley TD. Mitochondria, manganese superoxide dismutase, and cancer. Antioxid Redox Signal. 2004;6:483–7.

    Article  PubMed  CAS  Google Scholar 

  4. Li N, Li N, Oberley TD, Oberley LW, Zhong W. Overexpression of manganese superoxide dismutase in DU145 human prostate carcinoma cells has multiple effects on cell phenotype. Prostate. 1998;35:221–33.

    Article  PubMed  CAS  Google Scholar 

  5. O'berley LW. Mechanism of the tumor suppressive effect of MnSOD overexpression. Beamed Pharmacother. 2005;5:143–8.

    Article  Google Scholar 

  6. Komatsy M, Kuroda M, Wang Y, St Clair D, Urano M, Akaki S, Asaumi J, Kawasaki S, Hiraki Y, Kanazawa S. Manganese superoxide dismutase overexpression changes plating efficiency bidirectionally according to change in redox for SaOS2 human osteosarcoma cell line. Int J Oncol. 2005;26:853–62.

    Google Scholar 

  7. Wang Y, Komatsy M, Gao XS, Asaumi J, Shibuya K, Kawasaki S, Akaki S, St Clair D, Hiraki Y, Kanazawa S. Hydrogen peroxide overload increases adriamycin-induced apoptosis of SaOS2FM, a manganese superoxide dismutase-overexpressing human osteosarcoma cell line. Int J Oncol. 2005;26:1291–300.

    PubMed  CAS  Google Scholar 

  8. Izutani R, Asano S, Imano M, Kuroda D, Kato M, Ohyanagi H. Expression of manganese superoxide dismutase in esophageal and gastric cancers. J Gastroenterol. 1998;6:816–22.

    Article  Google Scholar 

  9. Epperly MW, Sikora C, Defilippi S, Bray J, Koe G, Liggitt D, Luketich JD, Greenberger JS. Plasmid/liposome transfer of the human manganese superoxide dismutase transgene prevents ionizing irradiation-induced apoptosis in human esophagus organ explant culture. Int J Cancer. 2000;90:128–37.

    Article  PubMed  CAS  Google Scholar 

  10. Sun GG, Wang YD, Chen LQ, Wang SJ, Liu GL, Yu XR, Cheng YJ, Liu Q. Novel cancer suppressor gene for esophageal cancer: manganese superoxide dismutase. Dis Esophagus. 2011;24:346–53.

    Article  Google Scholar 

  11. Schiffman SC, Li Y, Xiao D, Li X, Aiyer HS, Martin RC. The resistance of esophageal adenocarcinoma to bile salt insult is associated with manganese superoxide dismutase expression. J Surg Res. 2011;171:623–30.

    Article  PubMed  CAS  Google Scholar 

  12. Ressel L, Poli A. Simultaneous double labelling of routinely processed paraffin tissue sections using combined immunoperoxidase, immunofluorescence, and digital image editing. Res Vet Sci. 2010;88:122–6.

    Article  PubMed  CAS  Google Scholar 

  13. Zhang Y, Smith BJ, OberlLey W. Enzymatic activity is necessary for the tumor-suppressive effects of MnSOD. Antioxid Redox Signal. 2006;8:1283–93.

    Article  PubMed  CAS  Google Scholar 

  14. Weydert CJ, Waugh TA, Ritchie JM, et al. Overexpression of manganese or copper zinc superoxide dismutase inhibits breast cancer growth. Free Radic Biol Med. 2006;41:226–37.

    Article  PubMed  CAS  Google Scholar 

  15. Smith Pearson PS, Kooshki M, Spitz DR, et al. Decreasing peroxiredoxin II expression decreases glutathione, alters cell cycle distribution, and sensitizes glioma cells to ionizing radiation and H2O2. Free Radic Biol Med. 2008;45:1178–89.

    Article  PubMed  CAS  Google Scholar 

  16. Possel H, Noack H, Augustin W, et al. 2,7-Dihydrodichlorofluoresceindiacetate as a fluorescent marker for peroxynitrite formation. FEBS Lett. 1997;416:175–8.

    Article  PubMed  CAS  Google Scholar 

  17. Mancini A, Borrelli A, Schiattarella A, et al. Tumor suppressive activity of a variant isoform of Mn superoxide dismutase released by a human liposarcoma cell line. Int J Cancer. 2006;119:932–43.

    Article  PubMed  CAS  Google Scholar 

  18. Yan T, Oberley LW, Zhong W, et al. Manganese-containing superoxide dismutase overexpression causes phenotypic reversion in SV-40 transformed human lung fibroblasts. Cancer Res. 1996;56:2864–71.

    PubMed  CAS  Google Scholar 

  19. Zwacka RM, Duds L, Epperly MW, et al. Increased manganese superoxide dismutase expression suppresses the malignant phenotype of human melanoma cells. Proc Natl Acad Sci U S A. 1993;90:3113–7.

    Article  Google Scholar 

  20. Zhong W, Oberley LW. Suppression of malignant phenotype of human glioma cells by overexpression of manganese superoxide dismutase. Oncogene. 1997;14:481–90.

    Article  PubMed  CAS  Google Scholar 

  21. Chen J, Lin GX, Tang F, et al. Effects of manganese superoxide dismutase transfection on the proliferation of SGC7901 gastric cancer cell. Fudan Univ J Med Sci. 2004;31:19–23.

    CAS  Google Scholar 

  22. Lau AT, He QY, Chiu JF. A proteome analysis of the arsenite response in cultured lung cells: evidence for in vitro oxidative stress-induced apoptosis. Biochem J. 2004;382:641–50.

    Article  PubMed  CAS  Google Scholar 

  23. LauAT CJF. Proteomic and biochemical analyses of in vitro carcinogen-induced lung cell transformation: synergism between arsenic and benzo[a]pyrene. Proteomics. 2006;6:1619–30.

    Article  Google Scholar 

  24. Lau AT, Wang Y, Chiu JF. Reactive oxygen species: current knowledge and applications in cancer research and therapeutic. J Cell Biochem. 2008;104:657–67.

    Article  PubMed  CAS  Google Scholar 

  25. Wang M, Kirk JS, Venkataraman S, et al. Manganese superoxide dismutase suppresses hypoxic induction of hypoxia-inducible factor-1a and vascular endothelial growth factor. Oncogene. 2005;24:8154–66.

    PubMed  CAS  Google Scholar 

  26. Ridnour LA, Oberley TD, Oberley LW. Tumor suppressive effects of MnSOD overexpression may involve imbalance in peroxide generation versus peroxide removal. Antioxid Redox Signal. 2004;6:501–12.

    Article  PubMed  CAS  Google Scholar 

  27. Holley AK, Dhar SK, Xu Y, et al. Manganese superoxide dismutase: beyond life and death. Amino Acids. 2012;42:139–58.

    Article  PubMed  CAS  Google Scholar 

  28. Urano M, Kuroda M, Reynolds R, et al. Expression of manganese superoxide dismutase reduces tumor control radiation dose: gene-radiotherapy. Cancer Res. 1995;55:2490–3.

    PubMed  CAS  Google Scholar 

  29. Borrelli A, Schiattarella A, Mancini R, et al. A recombinant MnSOD is radioprotective for normal cells and radiosensitizing for tumor cells. Free Radic Biol Med. 2009;46:110–6.

    Article  PubMed  CAS  Google Scholar 

  30. Dhar SK, St Clair DK. Manganese superoxide dismutase regulation and cancer. Free Radic Biol Med. 2012;52(11–12):2209–22.

    Article  PubMed  CAS  Google Scholar 

  31. Dhar SK, Tangpong J, Chaiswing L, et al. Manganese superoxide dismutase is a p53-regulated gene that switches cancers between early and advanced stages. Cancer Res. 2011;71(21):6684–9665.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported, in part, by grants from the National Natural Science Foundation of China (#30,540,005), the Ministry of Personnel for the High-Level Talent Returned from Overseas (#Guo-Ren-Ting-Fa [2005]-118), the Starting Fund by the Ministry of Education for Personnel Returning from Abroad (#Jiao-Wai-Si-Liu [2008]-101), and Funded Projects on the Featured Disciplines (group) in the Institutions of Higher Learning in Hebei Province (#Ji-Jiao-Gao [2005]-52).

Conflict of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yadi Wang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sun, G., Wang, Y., Hu, W. et al. Effects of manganese superoxide dismutase (MnSOD) expression on regulation of esophageal cancer cell growth and apoptosis in vitro and in nude mice. Tumor Biol. 34, 1409–1419 (2013). https://doi.org/10.1007/s13277-012-0622-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-012-0622-x

Keywords

Navigation