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Open Life Sciences

formerly Central European Journal of Biology

Editor-in-Chief: Ratajczak, Mariusz

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IMPACT FACTOR 2016 (Open Life Sciences): 0.448

CiteScore 2016: 1.02

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Volume 5, Issue 5 (Oct 2010)


Superoxide dismutase mRNA and protein level in human colorectal cancer

Michał Skrzycki
  • Chair and Department of Biochemistry, Warsaw Medical University, 02-097, Warsaw, Poland
  • Email:
/ Monika Majewska
  • Chair and Department of Biochemistry, Warsaw Medical University, 02-097, Warsaw, Poland
  • Email:
/ Hanna Czeczot
  • Chair and Department of Biochemistry, Warsaw Medical University, 02-097, Warsaw, Poland
  • Email:
Published Online: 2010-08-20 | DOI: https://doi.org/10.2478/s11535-010-0054-9


Impairments of antioxidant enzyme expression are often concomitant with the onset of cancer. Due to epigenetic factors causing an inflammatory state the gastrointestinal tract can become exposed to reactive oxygen species. The purpose of our work was to evaluate mRNA and protein levels of superoxide dismutase isoenzymes in human colorectal adenocarcinoma due to its clinical advancement, and in colorectal cancer liver metastases. Evaluation of SOD expression in regard to CRC advancement, seems useful for clinical applications due to different tumor cells sensitivity to reactive oxygen species based treatment. Studies were conducted on a group of 27 patients: 15 diagnosed with colorectal adenocarcinoma and 12 diagnosed with colorectal cancer liver metastases. The mRNA level was determined by RT-PCR, and protein level by Western blotting. We observed significant (P≤0.05) changes of mRNA and protein level of SOD isoenzymes in subsequent stages of colorectal adenocarcinoma advancement and in colorectal cancer liver metastases. Differences in mRNA and protein level of SOD isoenzymes in colorectal adenocarcinoma and its liver metastases indicates that SOD participate in adaptation of tumor cells to oxidative stress, and maintain certain level of ROS, necessary for appropriate cell proliferation. Expression of superoxide dismutase isoenzymes seems to be regulated not only at transcriptional level, but also posttranscriptional.

Keywords: SOD isoenzymes; Expression; Oxidative stress; Colorectal cancer; Metastases

  • [1] Benson A.B. 3rd, Epidemiology, disease progression, and economic burden of colorectal cancer, J. Manag. Care Pharm., 2007, 13, S5–S18 Google Scholar

  • [2] Ballinger AB., Anggiansah C., Colorectal cancer, BMJ, 2007, 335, 715–718 http://dx.doi.org/10.1136/bmj.39321.527384.BECrossrefGoogle Scholar

  • [3] Soreide K., Janssen EA., Soiland H., Korner H., Baak J.P., Microsatellite instability in colorectal cancer, Br. J. Surg., 2006, 93, 395–406 http://dx.doi.org/10.1002/bjs.5328CrossrefGoogle Scholar

  • [4] Thibodeau S.N., Bren G., Schaid D., Microsatellite instability in cancer of the proximal colon, Science, 1993, 260, 816–819 http://dx.doi.org/10.1126/science.8484122CrossrefGoogle Scholar

  • [5] Worthley D.L., Whitehall V.L., Spring K.J., Leggett B.A., Colorectal carcinogenesis: road maps to cancer, World J. Gastroenterol., 2007, 13, 3784–3791 Google Scholar

  • [6] Grady W.M., Genomic instability and colon cancer, Cancer Metastasis Rev., 2004, 23, 11–27 http://dx.doi.org/10.1023/A:1025861527711CrossrefGoogle Scholar

  • [7] Hampel H., Frankel W.L., Martin E., Arnold M., Khanduja K., Kuebler P., Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer), N. Engl. J. Med., 2005, 352, 1851–1860 http://dx.doi.org/10.1056/NEJMoa043146CrossrefGoogle Scholar

  • [8] Hoeijmakers J.H., Genome maintenance mechanisms for preventing cancer, Nature, 2001, 411, 366–374 http://dx.doi.org/10.1038/35077232CrossrefGoogle Scholar

  • [9] Hsu S.M., Chen Y.C., Jiang M.C., 17 beta-estradiol inhibits tumor necrosis factor-alpha-induced nuclear factor-kappa B activation by increasing nuclear factor-kappa B p105 level in MCF-7 breast cancer cells, Biochem. Biophys. Res. Commun., 2000, 279, 7–52 http://dx.doi.org/10.1006/bbrc.2000.3891CrossrefGoogle Scholar

  • [10] Jass J.R., Whitehall V.L., Young J., Leggett B.A., Emerging concepts in colorectal neoplasia, Gastroenterology, 2002, 123, 862–876 http://dx.doi.org/10.1053/gast.2002.35392CrossrefGoogle Scholar

  • [11] Kawanishi S., Hiraku Y., Oikawa S., Mechanism of guanine-specific DNA damage by oxidative stress and its role in carcinogenesis and aging, Mutat. Res., 2001, 488, 65–76 http://dx.doi.org/10.1016/S1383-5742(00)00059-4CrossrefGoogle Scholar

  • [12] Williams G.M., Jeffrey A.M., Oxidative DNA damage: endogenous and chemically induced, Regul. Toxicol. Pharmacol., 2000, 32, 283–292 http://dx.doi.org/10.1006/rtph.2000.1433CrossrefGoogle Scholar

  • [13] Cheng K.C., Cahill D.S., Kasai H., Nishimura S., Loeb L.A., 8-Hydroxyguanine, an abundant form of oxidative DNA damage, causes G—T and A—C substitutions, J. Biol. Chem., 1992, 267, 166–172 Google Scholar

  • [14] Fridovich I., Superoxide anion radical (O2-), superoxide dismutases, and related matters, J. Biol. Chem., 1997, 272, 18515–18517 http://dx.doi.org/10.1074/jbc.272.30.18515CrossrefGoogle Scholar

  • [15] Zelko I.N., Mariani T.J., Folz R.J., Superoxide dismutase multigene family: A comparison of the Cu,ZnSOD (sod1), Mn-SOD (sod2), and EC-SOD (sod3) gene structures, evolution, and expression, Free Radic. Biol. Med., 2002, 33, 337–349 http://dx.doi.org/10.1016/S0891-5849(02)00905-XCrossrefGoogle Scholar

  • [16] Oberley L.W., Buettner G.R., Role of Superoxide Dismutase in Cancer: A Review, Cancer Res., 1979, 39, 1141–1149 Google Scholar

  • [17] Nicco C., Laurent A., Chereau C., Weill B., Batteux F., Differential modulation of normal and tumor cell proliferation by reactive oxygen species, Biomed. Pharmacother., 2005, 59, 169–174 http://dx.doi.org/10.1016/j.biopha.2005.03.009CrossrefGoogle Scholar

  • [18] Van Driel B.E., Lyon H., Hoogenraad D.C., Anten S., Hansen U., Van Noorden CJ., Expression of CuZn- and Mn-superoxide dismutase in human colorectal neoplasms, Free Radic. Biol. Med., 1997, 23, 435–444 http://dx.doi.org/10.1016/S0891-5849(97)00102-0CrossrefGoogle Scholar

  • [19] Janssen A.M., Bosman C.B., Kruidenier L., Griffioen G., Lamers C.B., van Krieken J.H., et al., Superoxide dismutases in the human colorectal cancer sequence, J. Cancer Res. Clin. Oncol., 1999, 125, 327–335 http://dx.doi.org/10.1007/s004320050282CrossrefGoogle Scholar

  • [20] Devi G.S., Prasad M.H., Saraswathi I., Raghu D., Rao D.N., Reddy P.P., Free radicals antioxidant enzymes and lipid peroxidation in different types of leukemias, Clin. Chim. Acta, 2000, 293, 53–62 http://dx.doi.org/10.1016/S0009-8981(99)00222-3CrossrefGoogle Scholar

  • [21] Hileman E.O., Liu J., Albitar M., Keating M.J., Huang P., Intrinsic oxidative stress in cancer cells: a biochemical basis for therapeutic selectivity, Cancer Chemother. Pharmacol., 2004, 53, 209–219 http://dx.doi.org/10.1007/s00280-003-0726-5CrossrefGoogle Scholar

  • [22] Santiard D., Inactivation of Cu,Zn-superoxide dismutase by free radicals derived from ethanol metabolism: a gamma radiolysis study, Free Radic. Biol. Med., 1995, 19, 121–127 http://dx.doi.org/10.1016/0891-5849(95)00008-LCrossrefGoogle Scholar

  • [23] Lowry O.H., Rosebrough N.J., Farr A.L., Randall R.J., Protein measurement with the Folin phenol reagent, J. Biol. Chem., 1951, 193, 265–275 Google Scholar

  • [24] Wang T., Zhang X., Li J.J., The role of NF-kappaB in the regulation of cell stress responses, Int. Immunopharmacol., 2002, 2, 1509–1520 http://dx.doi.org/10.1016/S1567-5769(02)00058-9CrossrefGoogle Scholar

  • [25] Skrzycki M., Czeczot H., Expression of superoxide dismutase genes in oxidative stress conditions, Post. Biol. Kom., 2004, 31, 81–92, (in Polish) http://dx.doi.org/10.1016/S0925-5214(03)00134-0CrossrefGoogle Scholar

  • [26] Loeb L.A., Mutator phenotype may be required for multistage carcinogenesis, Cancer Res., 1991, 51, 3075–3079 Google Scholar

  • [27] Visner G.A., Dougall W.C., Wilson J.M., Burr I.A., Nick H.S., Regulation of manganese superoxide dismutase by lipopolysaccharide, interleukin-1, and tumor necrosis factor. Role in the acute inflammatory response, J. Biol. Chem., 1990, 265, 2856–2864 Google Scholar

  • [28] Wong G.H.W., Goeddel D.V., Induction of manganous superoxide dismutase by tumor necrosis factor: possible protective mechanism, Science (Washington DC), 1988, 242, 941–944 http://dx.doi.org/10.1126/science.3263703CrossrefGoogle Scholar

  • [29] Skrzydlewska E., Sulkowski S., Koda M., Zalewski B., Kanczuga-Koda L., Sulkowska M., Lipid peroxidation and antioxidant status in colorectal cancer, World J. Gastroenterol., 2005, 11, 403–406 Google Scholar

  • [30] Nishimura H., Sanaka T., Nihei H., Nishikawa M., Aikawa E., Mechanism of elevated local oxidant stress in early anti-glomerular basement membrane nephritis: an evaluation of oxidant production and superoxide dismutase expression, Nippon Jinzo Gakkai Shi, 1996, 38, 441–448 Google Scholar

  • [31] Ahlemeyer B., Bauerbach E., Plath M., Steuber M., Heers C., Tegtmeier F., et al., Retinoic acid reduces apoptosis and oxidative stress by preservation of SOD protein level, Free Radic. Biol. Med., 2001, 30, 1067–1077 http://dx.doi.org/10.1016/S0891-5849(01)00495-6CrossrefGoogle Scholar

  • [32] Monje M.L., Chatten-Brown J., Hye S.E., Raley-Susman K.M., Free radicals are involved in the damage to protein synthesis after anoxia/aglycemia and NMDA exposure, Brain Res., 2000, 28, 172–182 http://dx.doi.org/10.1016/S0006-8993(99)02404-XCrossrefGoogle Scholar

  • [33] Niu C.S., Chang C.K., Lin L.S., Jou S.B., Kuo D.H., Liao S.S., et al., Modification of superoxide dismutase (SOD) mRNA and activity by a transient hypoxic stress in cultured glial cells, Neurosci. Lett., 1998, 251, 145–148 http://dx.doi.org/10.1016/S0304-3940(98)00506-0CrossrefGoogle Scholar

  • [34] Tsan M.F., White J.E., Shaffer J.B., Molecular basis for tumor necrosis factor-induced increase in pulmonary superoxide dismutase activities, Am. J. Physiol., 1990, 259, L506–L512 Google Scholar

  • [35] Santillo M., Mondola P., Serù R., Annella T., Cassano S., Ciullo I., et al., Opposing functions of Ki- and Ha-Ras genes in the regulation of redox signals, Curr. Biol., 2001, 11, 614–619 http://dx.doi.org/10.1016/S0960-9822(01)00159-2CrossrefGoogle Scholar

  • [36] Antunes F., Cadenas E., Cellular titration of apoptosis with steady state concentrations of H2O2: submicromolar levels of H2O2 induce apoptosis through Fenton chemistry independent of the cellular thiol state, Free Radic. Biol. Med., 2001, 30, 1008–1018 http://dx.doi.org/10.1016/S0891-5849(01)00493-2CrossrefGoogle Scholar

  • [37] Suresh A., Guedez L., Moreb J., Zucali J., Overexpression of manganese superoxide dismutase promotes survival in cell lines after doxorubicin treatment, Br. J. Haematol., 2003, 120, 457–463 http://dx.doi.org/10.1046/j.1365-2141.2003.04074.xCrossrefGoogle Scholar

  • [38] StClair D., Zhao Y., Chaiswing L., Oberley T., Modulation of skin tumorigenesis by SOD, Biomed. Pharmacother., 2005, 59, 209–214 http://dx.doi.org/10.1016/j.biopha.2005.03.004CrossrefGoogle Scholar

  • [39] Oberley L.W., Mechanism of the tumor suppresive effect of MnSOD overexpression, Biomed. Pharmacother., 2005, 59, 143–148 http://dx.doi.org/10.1016/j.biopha.2005.03.006CrossrefGoogle Scholar

  • [40] Dominguez A., Modifying superoxide dismutase for improved biopharmaceutical properties, Biotecnologia Aplicada, 2006, 23, 17–21 Google Scholar

  • [41] Szatrowski T.P., Nathan C.F., Production of large amounts of hydrogen peroxide by human tumor cells, Cancer Res., 1991, 51, 794–798 Google Scholar

  • [42] Golab J., Nowis D., Skrzycki M., Czeczot H., Baranczyk-Kuzma A., Wilczynski GM, et al., Antitumor effects of photodynamic therapy are potentiated by 2-methoxyestradiol — a superoxide dismutase inhibitor, J. Biol. Chem., 2003, 278, 407–414 http://dx.doi.org/10.1074/jbc.M209125200Google Scholar

About the article

Published Online: 2010-08-20

Published in Print: 2010-10-01

Citation Information: Open Life Sciences, ISSN (Online) 2391-5412, DOI: https://doi.org/10.2478/s11535-010-0054-9.

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© 2010 Versita Warsaw. This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License. BY-NC-ND 3.0

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