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ROS mediate selenite-induced apoptosis in colon cancer cells

  • Research Article
  • Published:
Central European Journal of Biology

Abstract

Selenite-induced oxidative stress and its relationship to mitochondrial apoptosis was studied in human adenocarcinoma HT-29 cells. It is shown that selenite induces caspase-dependent apoptosis, which is mediated by mitochondria via released cytochrome c, apoptosis-inducing factor (AIF) and Smac/Diablo. Selenite activates stress kinases p38 and JNK while suppressing reduced glutathione (GSH) and thioredoxin reductase (TrxR) levels, transiently inducing heme oxygenase (HO-1) system as well as reducing Akt expression. Pre-treatment of cells with selected antioxidants and stress kinase inhibitors significantly prevented selenite-induced cell death, thereby implicating oxidative stress as a direct (Bax) as well as indirect (via kinases) cause of HT-29 cells demise. These results thus demonstrate for the first time active proapoptotic and anti-survival effects of selenite in colon cancer cells.

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References

  1. Harrison P.R., Lanfear J., Wu L., Fleming J., McGarry L., Blower L., Chemopreventive and growth inhibitory effects of selenium, Biomed. Environ. Sci., 1997, 10, 235–245

    CAS  PubMed  Google Scholar 

  2. Rikiishi H., Apoptotic cellular events for selenium compounds involved in cancer prevention, J. Bioenerg. Biomembr., 2007, 39, 91–98

    Article  CAS  PubMed  Google Scholar 

  3. Brenneisen P., Steinbrenner H., Sies H., Selenium, oxidative stress, and health aspects, Mol. Aspects Med., 2005, 26, 256–267

    Article  CAS  PubMed  Google Scholar 

  4. Clark L.C., Combs G.F. Jr., Turnbull B.W., Slate E.H., Chalker D.K., Chow J., et al., Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group, JAMA, 1996, 276, 1957–1963

    CAS  Google Scholar 

  5. Meuillet E., Stratton S., Cherukuri D., Goulet A.-C., Kagey J., Porterfield B., et al., Chemoprevention of prostate cancer with selenium: An update on current clinical trials and preclinical findings, J. Cell. Biochem., 2004, 91, 443–458

    Article  CAS  PubMed  Google Scholar 

  6. Zeng H., Davis C.D., Down-regulation of proliferating cell nuclear antigen gene expression occurs during cell cycle arrest induced by human fecal water in colonic HT-29 cells, J. Nutr., 2003, 133, 2682–2687

    CAS  PubMed  Google Scholar 

  7. Jonsson-Videsater K., Bjorkhem-Bergman L., Hossain A., Soderberg A., Eriksson L., Paul C., et al., Selenite-induced apoptosis in doxorubicin-resistant cells and effects on the thioredoxin system, Biochem. Pharmacol., 2004, 67, 513–522

    Article  PubMed  Google Scholar 

  8. Li S., Zhou Y., Wang R., Zhang H., Dong Y., Ip C., Selenium sensitizes MCF-7 breast cancer cells to doxorubicin-induced apoptosis through modulation of phospho-Akt and its downstream substrates, Mol. Cancer Ther., 2007, 6, 1031–1038

    Article  CAS  PubMed  Google Scholar 

  9. Zhong W., Oberley T.D., Redox-mediated effects of selenium on apoptosis and cell cycle in the LNCaP human prostate cancer cell line, Cancer Res., 2001, 61, 7071–7078

    CAS  PubMed  Google Scholar 

  10. Yu R.A., Yang C.F., Chen X.M., DNA damage, apoptosis and C-myc, C-fos, and C-jun overexpression induced by selenium in rat hepatocytes, Biomed. Environ. Sci., 2006, 19, 197–204

    CAS  PubMed  Google Scholar 

  11. Zhu Y., Xu H., Huang K., Mitochondrial permeability transition and cytochrome c release induced by selenite., J. Inorg. Biochem., 2002, 90, 43–50

    Article  CAS  PubMed  Google Scholar 

  12. Huang F., Nie C., Yang Y., Yue W., Ren Y., Shang Y., et al., Selenite induces redox-dependent Bax activation and apoptosis in colorectal cancer cells, Free Radic. Biol. Med., 2009, 46, 1186–1196

    Article  CAS  PubMed  Google Scholar 

  13. Song G., Ouyang G., Bao S., The activation of Akt/PKB signaling pathway and cell survival, J. Cell. Mol. Med., 2005, 9, 59–71

    Article  CAS  PubMed  Google Scholar 

  14. Rudolf E., Kralova V., Cervinka M., Selenium and colon cancer—from chemoprevention to new treatment modality, Anticancer Agents Med. Chem., 2008, 8, 598–602

    CAS  PubMed  Google Scholar 

  15. Wang H., Yang X., Zhang Z., Xu H., Both calcium and ROS as common signals mediate Na2SeO3-induced apoptosis in SW480 human colonic carcinoma cells, J. Inorg. Biochem., 2003, 97, 221–230

    Article  CAS  PubMed  Google Scholar 

  16. Zhou N., Xiao H., Li T.K., Nur-E-Kamal A., Liu L.F., DNA damage-mediated apoptosis induced by selenium compounds., J. Biol. Chem., 2003, 278, 29532–29537

    Article  CAS  PubMed  Google Scholar 

  17. Stewart M.S., Davis R.L., Walsh L.P., Pence B.C., Induction of differentiation and apoptosis by sodium selenite in human colonic carcinoma cells (HT29), Cancer Lett., 1997, 117, 35–40

    Article  CAS  PubMed  Google Scholar 

  18. Kim Y.S., Jhon D.Y., Lee K.Y., Involvement of ROS and JNK1 in selenite-induced apoptosis in Chang liver cells, Exp. Mol. Med., 2004, 36, 157–164

    CAS  PubMed  Google Scholar 

  19. Li G.X., Hu H., Jiang C., Schuster T., Lu J., Differential involvement of reactive oxygen species in apoptosis induced by two classes of selenium compounds in human prostate cancer cells, Int. J. Cancer, 2007, 120, 2034–2043

    Article  CAS  PubMed  Google Scholar 

  20. Wang H.T., Yang X.L., Zhang Z.H., Lu J.L., Xu H.B., Reactive oxygen species from mitochondria mediate SW480 cells apoptosis induced by Na2SeO3, Biol. Trace Elem. Res., 2002, 85, 241–254

    Article  CAS  PubMed  Google Scholar 

  21. Zeng H., Botnen J.H., Johnson L.K., A selenium-deficient Caco-2 cell model for assessing differential incorporation of chemical or food selenium into glutathione peroxidase, Biol. Trace Elem. Res., 2008, 123, 98–108

    Article  CAS  PubMed  Google Scholar 

  22. Han B., Wei W., Hua F., Cao T., Dong H., Yang T., et al., Requirement for ERK activity in sodium selenite-induced apoptosis of acute promyelocytic leukemia-derived NB4 cells, J. Biochem. Mol. Biol., 2007, 40, 196–204

    CAS  PubMed  Google Scholar 

  23. Ranawat P., Bansal M.P., Decreased glutathione levels potentiate the apoptotic efficacy of selenium: possible involvement of p38 and JNK MAPKs—in vitro studies, Mol. Cell. Biochem., 2008, 309, 21–32

    Article  CAS  PubMed  Google Scholar 

  24. Lin A., Activation of the JNK signaling pathway: breaking the brake on apoptosis, Bioessays, 2003, 25, 17–24

    Article  PubMed  Google Scholar 

  25. Park H.S., Park E., Kim M.S., Ahn K., Kim I.Y., Choi E.J., Selenite inhibits the c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) through a thiol redox mechanism, J. Biol. Chem., 2000, 275, 2527–2531

    Article  CAS  PubMed  Google Scholar 

  26. Zou Y., Niu P., Yang J., Yuan J., Wu T., Chen X., The JNK signaling pathway is involved in sodium-selenite-induced apoptosis mediated by reactive oxygen in HepG2 cells, Cancer Biol. Ther., 2008, 7, 689–696

    Article  CAS  PubMed  Google Scholar 

  27. Liu B., Chen Y., St Clair D.K., ROS and p53: a versatile partnership, Free Radic. Biol. Med., 2008, 44, 1529–1535

    Article  CAS  PubMed  Google Scholar 

  28. Gayet J., Zhou X.P., Duval A., Rolland S., Hoang J.M., Cottu P., et al., Extensive characterization of genetic alterations in a series of human colorectal cancer cell lines, Oncogene, 2001, 20, 5025–5032

    Article  CAS  PubMed  Google Scholar 

  29. Anguiano-Hernandez Y.M., Chartier A., Huerta S., Smac/DIABLO and colon cancer, Anticancer Agents Med. Chem., 2007, 7, 467–473

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Medical Biology and Genetics, Charles University in Prague, Faculty of Medicine in Hradec Králové, 500 38, Hradec Králové, Czech Republic

    Věra Králová, Miroslav Červinka & Emil Rudolf

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  1. Věra Králová
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  2. Miroslav Červinka
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  3. Emil Rudolf
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Correspondence to Emil Rudolf.

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Králová, V., Červinka, M. & Rudolf, E. ROS mediate selenite-induced apoptosis in colon cancer cells. cent.eur.j.biol. 5, 166–177 (2010). https://doi.org/10.2478/s11535-010-0007-3

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  • DOI: https://doi.org/10.2478/s11535-010-0007-3

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