Korean J Urol.  2007 Sep;48(9):921-926. 10.4111/kju.2007.48.9.921.

Expression of Antioxidant Enzymes(Catalase, Superoxide Dismutase, and Glutathione Peroxidase) in Human Bladder Cancer

• Jeon SH
• Park JH
• Chang SG

• KMID: 2061292
• DOI: http://doi.org/10.4111/kju.2007.48.9.921

Abstract

PURPOSE
Intrinsic antioxidant enzymes(AOE) are essential for protection against potential cellular damage by reactive oxygen species(ROS), which affect many biological processes including carcinogenesis. The aim of the present study was to characterize the expression of antioxidant enzymes in human bladder cancer tissue and to evaluate the relationship with histopathological characteristics.
MATERIALS AND METHODS
Immunohistochemical stainingfor catalase, superoxide dismutase(SOD), and glutathione peroxidase(GPx) was performed on formalin-fixed, paraffin-embedded tissues obtained from 75 bladder cancersand 30 normal bladders. The degree of AOE expression was compared with cancer invasiveness or the cell grade.
RESULTS
The expression of catalase and SOD were significantly lower in cancer tissue than in normal bladder tissue(44% vs 73.3%, p=0.012; 49.3% vs 80%, p=0.007, respectively) but GPx expression was not significantly different(45.3% vs 63.3%, p=0.146). Catalase and SOD expression were significantly lower in invasive transitional cell carcinomas than in superficial transitional cell carcinomas(32.4% vs 53.7%, p=0.034; 32.4% vs 63.4%, p=0.014, respectively), but again GPx expression was not significantly different(38.2% vs 51.2%, p=0.26). Moreover, no significant difference was observed between the expression of all three enzymes and the cancer cell grade.
CONCLUSIONS
Down-regulation of the antioxidant enzyme system, as indicated by the expression of catalase and SOD, appears to be related with carcinogenesis and progression in bladder cancer.

Keyword

Antioxidants; Immunohistochemistry; Urinary bladder neoplasms

MeSH Terms

Antioxidants
Biological Processes
Carcinogenesis
Carcinoma, Transitional Cell
Catalase
Down-Regulation
Glutathione*
Humans*
Immunohistochemistry
Oxygen
Superoxide Dismutase*
Superoxides*
Urinary Bladder Neoplasms*
Urinary Bladder*
Antioxidants
Catalase
Glutathione
Oxygen
Superoxide Dismutase
Superoxides

Figure

• 

  Fig. 1 Immunohistochemical analysis of the antioxidant enzymes in transitional cell carcinoma of the bladder and adjacent normal transitional epithelium. (A) Strong staining for catalase is seen in normal transitional epithelial cells. (B) Staining for catalase is nearlyundetectable in transitional cell carcinoma. (C) Strong staining for Cu, Zn-superoxide dismutase is seen in normal transitional epithelial cells. (D) Light staining for Cu, Zn-superoxide dismutase is seen in transitional cell carcinoma. (E) Light staining for glutathione peroxidase is seen in normal transitional epithelial cells. (F) Staining for glutathione peroxidase is nearly undetectable in transitional cell carcinoma.

Reference

1. Sun Y, Oberley LW. Redox regulation of transcriptional activators. Free Radic Biol Med. 1996. 21:335–348.

2. Freeman BA, Crapo JD. Biology of disease: free radicals and tissue injury. Lab Invest. 1982. 47:412–426.

3. Rautalahti M, Huttunen J. Antioxidants and carcinogenesis. Ann Med. 1994. 26:435–441.

4. McCord JM, Fridovich I. Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). J Biol Chem. 1969. 244:6049–6055.

5. Percy ME. Catalase: an old enzyme with a new role? Can J Biochem Cell Biol. 1984. 62:1006–1014.

6. Mills GC. Hemoglobin catabolism. I. Glutathione peroxidase, an erythrocyte enzyme which protects hemoglobin from oxidative breakdown. J Biol Chem. 1957. 229:189–197.

7. Cerutti PA. Oxy-radicals and cancer. Lancet. 1994. 344:862–863.

8. Burdon RH, Gill V, Rice-Evans C. Oxidative stress and tumour cell proliferation. Free Radic Res Commun. 1990. 11:65–76.

9. Li JJ, Oberley LW, St Clair DK, Ridnour LA, Oberley TD. Phenotypic changes induced in human breast cancer cells by overexpression of manganese-containing superoxide dismutase. Oncogene. 1995. 10:1989–2000.

10. Tew K. Glutathione-associated enzymes in anticancer drug resistance. Cancer Res. 1994. 54:4313–4320.

11. Church SL, Grant JW, Ridnour LA, Oberley LW, Swanson PE, Meltzer PS, et al. Increased manganese superoxide dismutase expression suppresses the malignant phenotype of human melanoma cells. Proc Natl Acad Sci USA. 1993. 90:3113–3117.

12. Urano M, Kuroda M, Reynolds R, Oberley TD, St Clair DK. Expression of manganese superoxide dismutase reduces tumor control radiation dose: gene-radiotherapy. Cancer Res. 1995. 55:2490–2493.

13. Oberley LW, Buettner GR. Role of superoxide dismutase in cancer: a review. Cancer Res. 1979. 39:1141–1149.

14. Oberley TD, Sempf JM, Oberley LW. Immunogold analysis of antioxidant enzymes in common renal cancers. Histol Histopathol. 1996. 11:153–160.

15. Cobbs CS, Levi DS, Aldape K, Israel MA. Manganese superoxide dismutase expression in human central nervous system tumors. Cancer Res. 1996. 56:3192–3195.

16. Shibanuma M, Kuroki T, Nose K. Induction of DNA replication and expression of proto-oncogenes c-myc and c-fos in quiescent Balb/3T3 cells by xanthine/xanthine oxidase. Oncogene. 1988. 3:17–21.

17. Hockenbery DM, Oltvai ZN, Yin XM, Milliman CL, Korsmeyer SJ. Bcl-2 functions in an antioxidant pathway to prevent apoptosis. Cell. 1993. 75:241–251.

18. Sun Y. Free radicals, antioxidant enzymes, and carcinogenesis. Free Radic Biol Med. 1990. 8:583–599.

19. Cao C, Leng Y, Kufe D. Catalase activity is regulated by c-Abl and Arg in the oxidative stress response. J Biol Chem. 2003. 278:29667–29675.

20. Kondo S, Toyokuni S, Iwasa Y, Tanaka T, Onodera H, Hiai H, et al. Persistent oxidative stress in human colorectal carcinoma, but not in adenoma. Free Radic Biol Med. 1999. 27:401–410.

21. Cullen JJ, Mitros FA, Oberley LW. Expression of antioxidant enzymes in diseases of the human pancreas: another link between chronic pancreatitis and pancreatic cancer. Pancreas. 2003. 26:23–27.

22. Zhong W, Oberley LW, Oberley TD, Yan T, Domann FE, St Clair DK. Inhibition of cell growth and sensitization to oxidative damage by overexpression of manganese superoxide dismutase in rat glioma cells. Cell Growth Differ. 1996. 7:1175–1186.