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Distinct effects of different concentrations of sodium selenite on apoptosis, cell cycle, and gene expression profile in acute promyeloytic leukemia-derived NB4 cells

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Abstract

Selenium at a low concentration has a chemopreventive role against cancer, while at a high concentration, it exerts a direct antitumor effect. However, the mechanisms remain elusive. In this article, we discovered that Na2SeO3 at 20 μmol/l concentration could significantly inhibit the proliferation of NB4 cells, affect the cell cycle distribution of cell population, and induce cellular changes characteristic of apoptotic cells, while this same compound at 2 μmol/l concentration had no such effects. The mechanisms underlying these overt differences caused by treatment of different concentrations of selenium were further investigated. cDNA microarray analysis showed that after treatment by 20 μmol/l Na2SeO3, 34 genes were changed in expression, while treatment by 2 μmol/l Na2SeO3 resulted in the changes of 29 genes. Nine genes were regulated in both groups, among which three showed opposite changes caused by 2 and 20 μmol/l Na2SeO3. The majority of regulated genes did not coincide between the two experiment groups. In conclusion, 2 and 20 μmol/l Na2SeO3 could have different effects on NB4 cells, and some genes might be involved in the underlying mechanisms. Our findings could provide basis for further uncovering the molecular mechanisms of the chemopreventive and antitumor effects of selenium and, in turn, for probing the rationality of treating leukemia with selenium.

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References

  1. Barrett JC, Kawasaki ES (2003) Microarrays: the use of oligonucleotides and cDNA for the analysis of gene expression. Drug Discov Today 8:134–141

    Article  PubMed  CAS  Google Scholar 

  2. Bellosillo B, Dalmau M, Colomer D, Gil J (1997) Involvement of CED-3/ICE proteases in the apoptosis of B-chronic lymphocytic leukemia cells. Blood 89:3378

    PubMed  CAS  Google Scholar 

  3. Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR, Sultan C (1976) Proposals for the classification of the acute leukaemias, French–American–British (FAB) co-operative group. Br J Haematol 33:451–458

    Article  PubMed  CAS  Google Scholar 

  4. Camacho LH, Soignet SL, Chanel S, Ho R, Heller G, Scheinberg DA, Ellison R, Warrell RP Jr (2000) Leukocytosis and the retinoic acid syndrome in patients with acute promyelocytic leukemia treated with arsenic trioxide. J Clin Oncol 18:2620–2625

    PubMed  CAS  Google Scholar 

  5. Chen GQ, Shi X-G, Tang W, Xiong S-M, Zhu J, Cai X, Han Z-G, Ni J-H, Shi G-Y, Jia P-M, Liu M-M, He K-L, Niu C, Ma J, Zhang P, Zhang T-D, Paul P, Waxman Sl, Wang Z-Y, Chen S-J, Chen Z (1997) Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL): I. As2O3 exerts dose-dependent dual effects on APL cells. Blood 89:3345–3353

    PubMed  CAS  Google Scholar 

  6. Diwadkar-Navsariwala V, Diamond AM (2004) The link between selenium and chemoprevention: a case for selenoproteins. J Nutr 134(11):2899–2902

    PubMed  CAS  Google Scholar 

  7. Duffield-Lillico AJ, Reid ME, Turnbull BW, Combs GF Jr, Slate EH, Fischbach LA, Marshall JR, Clark LC (2002). Baseline characteristics and the effect of selenium supplementation on cancer incidence in a randomized clinical trial: a summary report of the nutritional prevention of cancer trial. Cancer Epidemiol Biomarkers Prev 11:630–639

    PubMed  CAS  Google Scholar 

  8. El-Bayoumy K (2001) The protective role of selenium on genetic damage and on cancer. Mutat Res 475:123–139

    PubMed  CAS  Google Scholar 

  9. El-Bayoumy K, Sinha R (2004) Mechanisms of mammary cancer chemoprevention by organoselenium compounds. Mutat Res 13:181–197

    Google Scholar 

  10. Fenaux P, Chomienne C, Degos L (2001) All-trans retinoic acid and chemotherapy in the treatment of acute promyelocytic leukemia. Semin Hematol 38:13–25

    Article  PubMed  CAS  Google Scholar 

  11. Kakizuka A, Miller WH Jr, Umesono K, Warrell RP Jr, Frankel SR (1991) Chromosomal translocation t(15;17) in human acute promyelocytic leukemia fuses RARα with a novel putative transcription factor, PML. Cell 66:663–674

    Article  PubMed  CAS  Google Scholar 

  12. Kastner P, Lawrence HJ, Waltzinger C, Ghyselinck NB, Chambon P, Chan S (2001) Positive and negative regulation of granulopoiesis by endogenous RARα. Blood 97:1314–1320

    Article  PubMed  CAS  Google Scholar 

  13. Kelly DL, Rizzino A (2000) DNA microarray analyses of genes regulated during the differentiation of embryonic stem cells. Mol Reprod Dev 56:113–123

    Article  PubMed  CAS  Google Scholar 

  14. Li J, Zuo L, Shen T, Zhang ZN (2002) Sodium selenite-induced oxidative stress and apoptosis in human acute promyelocytic leukemia NB4 cells. Yao Xue Xue Bao 37(9):677–681

    PubMed  CAS  Google Scholar 

  15. Li J, Zuo L, Shen T, Xu CM, Zhang ZN (2003) Induction of apoptosis by sodium selenite in human acute promyelocytic leukemia NB4 cells: involvement of oxidative stress and mitochondria. J Trace Elem Med Biol 17:19–26

    Article  PubMed  CAS  Google Scholar 

  16. Neve J (2002) Selenium as a nutraceutical: how to conciliate physiological and supra-nutritionaleffects for an essential trace element. Curr Opin Clin Nutr Metab Care 5:659–663

    Article  PubMed  CAS  Google Scholar 

  17. Raich PC, Lu J, Thompson HJ, Combs GF Jr (2001) Selenium in cancer prevention: clinical issues and implications. Cancer Invest 19:540–553

    Article  PubMed  CAS  Google Scholar 

  18. Rayman MP (2000) The importance of selenium to human health. Lancet 356:233–241

    Article  PubMed  CAS  Google Scholar 

  19. Rowley JD, Golomb HM, Vardiman J, Fukuhara S, Dougherty C, Potter D (1977) Further evidence for a non-random chromosomal abnormality in acute promyelocytic leukemia. Int J Cancer 20:869–872

    Article  PubMed  CAS  Google Scholar 

  20. Sargent JM, Taylor CG (1989) Appraisa of the MTT assay as a rapid test of chemosenitivity in acute myeloid leukemia. Br J Cancer 60:206–210

    PubMed  CAS  Google Scholar 

  21. Shao W, Fanelli M, Ferrara FF, Riccioni R, Rosenauer A, Davison K, Lamph WW, Waxman S, Pelicci PG, Lo Coco F, Avvisati G, Testa U, Peschle C, Gambacorti-Passerini C, Nervi C, Miller WH Jr (1998) Arsenic trioxide as aninducer of apoptosis and loss of PML/RARα protein in acute promyelocytic leukemia cells. J Natl Cancer Inst 90:124–133

    Article  PubMed  CAS  Google Scholar 

  22. Slack JL, Rusiniak ME (2000) Current issues in the management of acute promyelocytic leukemia. Ann Hematol 79:227–238

    Article  PubMed  CAS  Google Scholar 

  23. Stratton MS, Reid ME, Schwartzberg G, Minter FE, Monroe BK, Alberts DS, Marshall JR, Ahmann FR (2003) Selenium and prevention of prostate cancer in high-risk men: the negative biopsy study. Anticancer Drugs 14:589–594

    Article  PubMed  CAS  Google Scholar 

  24. Zuo L, Li J, Shen T, Zhang ZN (2002) The comparison between the mechanisms of sodium selenite induced apoptosis and arsenic trioxide induced apoptosis in human acute promyelocytic leukemia cell line NB4 cells. Zhongguo Shi Yan Xue Ye Xue Za Zhi 10:195–200

    PubMed  Google Scholar 

  25. Zuo L, Li J, Yang Y, Wang X, Shen T, Xu CM, Zhang ZN (2004) Sodium selenite induces apoptosis in acute promyelocytic leukemia-derived NB4 cells by a caspase-3-dependent mechanism and a redox pathway different from that of arsenic trioxide. Ann Hematol 83(12):751–758

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

This work was supported by grants from National Natural Sciences Foundation of China (no. 30370348), Doctoral Point Foundation of National Educational Committee (no. 20010023029), and Natural Sciences Foundation of Beijing (no. 7032034).

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Correspondence to Cai-Min Xu.

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Cao, TM., Hua, FY., Xu, CM. et al. Distinct effects of different concentrations of sodium selenite on apoptosis, cell cycle, and gene expression profile in acute promyeloytic leukemia-derived NB4 cells. Ann Hematol 85, 434–442 (2006). https://doi.org/10.1007/s00277-005-0046-4

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  • DOI: https://doi.org/10.1007/s00277-005-0046-4

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