Selenium as a mineral with anti-cancer properties

Document Type : Review

Authors

1 Department of Biochemistry, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran

2 Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

Abstract

Selenium (Se) is a trace element necessary for the proper functioning of organisms that have recently gained substantial attention due to its promising chemotherapeutic potential in cancer prevention and treatment. Besides providing routine anticancer treatments, Se supplementation has been shown to enhance the suitability of standard chemotherapeutic approaches with limited side effects and without reducing the treatment effectiveness, thus improving the patients' general conditions. The smallest changes in the Se content may cause its deficiency or excess. Therefore, a supplementation has to be carefully and cautiously administered.
Nevertheless, Se mechanisms of potentially anticancer properties are not fully understood. The relevant research has shown that its properties may correlate with its antioxidant protection, enhanced immune surveillance, augmented carcinogen detoxification, modulation of cell proliferation (cell cycle and apoptosis), and inhibitions of angiogenesis and tumor cell invasion and migration.
It is worthy to mention that Se biological activity, potential anticancer properties, and compounds are highly dependent on its speciation, chemical form, and specific metabolic pathways of the target cells and tissues.
Elucidating and deepening our knowledge of Se and its properties will help in designing and optimizing its compounds with more specific antitumor properties for their possible future applications in the treatment of cancer. This review surveys the global cancer status and provides progress in the current understanding of the molecular mechanisms that clarify the potential anticancer effects of Se and its compounds.

Keywords


  1. Research AIfC, International WCRF. Food, nutrition and the prevention of cancer: a global perspective: American Institute for Cancer Research; 1997.
  2. Frieden E. New perspectives on the essential trace elements. J Chem Educ. 1985;62(11):917. doi:10.1021/ed062p917
  3. Navarro-Alarcon M, Cabrera-Vique C. Selenium in food and the human body: A review. Sci Total Environ. 2008;400(1-3):115-41. doi:10.1016/j.scitotenv.2008.06.024 PMid:18657851
  4. Kieliszek M, Błażejak S. Selenium: significance, and outlook for supplementation. Nutrition. 2013;29(5):713-8. doi:10.1016/j.nut.2012.11.012 PMid:23422539
  5. Holben DH, Smith AM. The diverse role of selenium within selenoproteins: a review. J Am Diet Assoc. 1999;99(7):836-43.doi:10.1016/S0002-8223(99)00198-4
  6. Weekley CM, Harris HH. Which form is that? The importance of selenium speciation and metabolism in the prevention and treatment of disease. Chem Soc Rev. 2013;42(23):8870-94. doi:10.1039/c3cs60272a PMid:24030774
  7. Brinkman M, Reulen RC, Kellen E, Buntinx F, Zeegers MP. Are men with low selenium levels at increased risk of prostate cancer? Eur J Cancer. 2006;42 (15): 2463-71. doi:10.1016/j.ejca.2006.02.027 PMid:16945521
  8. Zhuo H, Smith AH, Steinmaus C. Selenium and lung cancer: a quantitative analysis of heterogeneity in the current epidemiological literature. Cancer Epidemiol Biomarkers Prev. 2004; 13(5):771-8.
  9. Amaral AF, Cantor KP, Silverman DT, Malats N. Selenium and bladder cancer risk: a meta-analysis. Cancer Epidemiol Biomarkers Prev. 2010;19(9):2407-15. doi:10.1158/1055-9965.EPI-10-0544 PMid:20807831 PMCid:PMC6982398
  10. Whanger P. Selenium and its relationship to cancer: an update. Br J Nutr. 2004;91(01):11-28. doi:10.1079/BJN20031015 PMid:14748935
  11. Clark LC, Combs GF, Turnbull BW, Slate EH, Chalker DK, Chow J, et al. Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin: a randomized controlled trial. JAMA. 1996;276(24):1957-63. doi:10.1001/jama.1996.03540240035027 PMid:8971064
  12. Lippman SM, Goodman PJ, Klein EA, Parnes HL, Thompson IM, Kristal AR, et al. Designing the selenium and vitamin E cancer prevention trial (SELECT). J Natl Cancer Inst. 2005;97(2):94-102. doi:10.1093/jnci/dji009 PMid:15657339
  13. Ip C, Dong Y, Ganther HE. New concepts in selenium chemoprevention. Cancer Metastasis Rev. 2002; 21 (3-4):281-9. doi:10.1023/A:1021263027659 PMid:12549766
  14. Lu J, Jiang C. Antiangiogenic activity of selenium in cancer chemoprevention: metabolite-specific effects. Nutr Cancer. 2001; 40 (1):64-73. doi:10.1207/S15327914NC401_12 PMid:11799926
  15. Lobanov AV, Hatfield DL, Gladyshev VN. Eukaryotic selenoproteins and selenoproteomes. Biochim Biophys Acta Gen Subj. 2009; 1790 (11): 1424-8. doi:10.1016/j.bbagen.2009.05.014 PMid:19477234 PMCid:PMC3471088
  16. Arnér ES. Selenoproteins-What unique properties can arise with selenocysteine in place of cysteine? Exp Cell Res. 2010;316(8): 1296-303. doi:10.1016/j.yexcr.2010.02.032 PMid:20206159
  17. Hatfield DL, Yoo M-H, Carlson BA, Gladyshev VN. Selenoproteins that function in cancer prevention and promotion. Biochim Biophys Acta Gen Subj. 2009; 1790 (11): 1541-5. doi:10.1016/j.bbagen.2009.03.001 PMid:19272412 PMCid:PMC2763959
  18. World Health Organization. The Global Burden of Disease: 2004 Update. Geneva: World Health Organization; 2008.
  19. Coleman MP, Quaresma M, Berrino F, Lutz JM, De Angelis R, Capocaccia R, et al. Cancer survival in five continents: a worldwide population-based study (CONCORD). Lancet Oncol. 2008;9(8):730-56.doi:10.1016/S1470-2045(08)70179-7
  20. Edwards BK, Ward E, Kohler BA, Eheman C, Zauber AG, Anderson RN, et al. Annual report to the nation on the status of cancer, 1975-2006, featuring colorectal cancer trends and impact of interventions (risk factors, screening, and treatment) to reduce future rates. Cancer. 2010;116(3):544-73. doi:10.1002/cncr.24760 PMid:19998273 PMCid:PMC3619726
  21. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69-90. doi:10.3322/caac.20107 PMid:21296855
  22. Wogan GN, Hecht SS, Felton JS, Conney AH, Loeb LA, editors. Environmental and chemical carcinogenesis. Semin Cancer Biol; 2004: doi:10.1016/j.semcancer.2004.06.010 PMid:15489140
  23. Lichtenstein AV. Cancer: evolutionary, genetic and epigenetic aspects. Clin Epigenetics. 2010;1(3):85. doi:10.1007/s13148-010-0010-6 PMid:22704202 PMCid:PMC3365664
  24. Weinberg R. The biology of cancer: Garland science; 2013.doi:10.1201/9780429258794
  25. Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002; 420(6917):860-7. doi:10.1038/nature01322 PMid:12490959 PMCid:PMC2803035
  26. Elzinga-Tinke JE, Dohle GR, Looijenga LH. Etiology and early pathogenesis of malignant testicular germ cell tumors: towards possibilities for preinvasive diagnosis. Asian J Androl. 2015; 17 (3):381-93.
  27. Grady WM, Markowitz SD. The molecular pathogenesis of colorectal cancer and its potential application to colorectal cancer screening. Dig Dis Sci. 2015; 60 (3): 762-72. doi:10.1007/s10620-014-3444-4 PMid:25492499 PMCid:PMC4779895
  28. Vecchio L, Seke Etet PF, Kipanyula MJ, Krampera M, Nwabo Kamdje AH. Importance of epigenetic changes in cancer etiology, pathogenesis, clinical profiling, and treatment: what can be learned from hematologic malignancies? Biochim Biophys Acta. 2013;1836(1):90-104. doi:10.1016/j.bbcan.2013.04.001 PMid:23603458
  29. Arbyn M, Anttila A, Jordan J, Ronco G, Schenck U, Segnan N, et al. European guidelines for quality assurance in cervical cancer screening. -summary document. Ann Oncol. 2010;21(3):448-58. doi:10.1093/annonc/mdp471 PMid:20176693 PMCid:PMC2826099
  30. Das SK, Menezes ME, Bhatia S, Wang XY, Emdad L, Sarkar D, et al. Gene therapies for cancer: strategies, challenges and successes. J Cell Physiol. 2015;230(2):259-71. doi:10.1002/jcp.24791 PMid:25196387 PMCid:PMC4363073
  31. Alberts S, Cervantes A, Van de Velde C. Gastric cancer: epidemiology, pathology and treatment. Ann Oncol. 2003;14 (90002):31-6. doi:10.1093/annonc/mdg726 PMid:12810455
  32. Herbst RS, Bajorin DF, Bleiberg H, Blum D, Hao D, Johnson BE, et al. Clinical Cancer Advances 2005: major research advances in cancer treatment, prevention, and screening-a report from the American Society of Clinical Oncology. J Clin Oncol. 2006; 24(1):190-205. doi:10.1200/JCO.2005.04.8678 PMid:16326753
  33. Crawford S. Anti-inflammatory/antioxidant use in long-term maintenance cancer therapy: a new therapeutic approach to disease progression and recurrence. Ther Adv Med Oncol. 2014; 6(2):52-68. doi:10.1177/1758834014521111 PMid:24587831 PMCid:PMC3932057
  34. Ascierto PA, Addeo R, Cartenì G, Daniele B, De Laurentis M, Ianniello GP, et al. The role of immunotherapy in solid tumors: report from the Campania Society of Oncology Immunotherapy (SCITO) meeting, Naples 2014. J Transl med. 2014;12(1):1. doi:10.1186/s12967-014-0291-1 PMid:25331657 PMCid:PMC4209076
  35. Westwood JA, Kershaw MH. Genetic redirection of T cells for cancer therapy. J Leukoc Biol. 2010; 87 (5): 791-803. doi:10.1189/jlb.1209824 PMid:20179152
  36. Huang Y, Goel S, Duda DG, Fukumura D, Jain RK. Vascular normalization as an emerging strategy to enhance cancer immunotherapy. Cancer Res. 2013;73(10):2943-8. doi:10.1158/0008-5472.CAN-12-4354 PMid:23440426 PMCid:PMC3655127
  37. Coates A, Abraham S, Kaye SB, Sowerbutts T, Frewin C, Fox R, et al. On the receiving end-patient perception of the side-effects of cancer chemotherapy. Eur J Cancer Clin Oncol. 1983;19 (2): 203-8.doi:10.1016/0277-5379(83)90418-2
  38. Shapiro CL, Recht A. Side effects of adjuvant treatment of breast cancer. N Engl J Med. 2001; 344 (26): 1997-2008. doi:10.1056/NEJM200106283442607 PMid:11430330
  39. Schultheiss TE, Lee WR, Hunt MA, Hanlon AL, Peter RS, Hanks GE. Late GI and GU complications in the treatment of prostate cancer. Int J Radiat Oncol Biol Phys. 1997;37(1):3-11.doi:10.1016/S0360-3016(96)00468-3
  40. Marijnen C, Kapiteijn E, Van de Velde C, Martijn H, Steup W, Wiggers T, et al. Acute side effects and complications after short-term preoperative radiotherapy combined with total mesorectal excision in primary rectal cancer: report of a multicenter randomized trial. J Clin Oncol. 2002;20(3):817-25. doi:10.1200/JCO.2002.20.3.817 PMid:11821466
  41. Swenson KK, Nissen MJ, Ceronsky C, Swenson L, Lee MW, Tuttle TM. Comparison of side effects between sentinel lymph node and axillary lymph node dissection for breast cancer. Ann Surg Oncol. 2002;9(8):745-53. doi:10.1007/BF02574496 PMid:12374657
  42. Stewart B, Wild C. World Cancer Report 2014: IARC Nonserial Publication. World Health Organization: Geneva. 2014.
  43. Workman P. Genomics and the second golden era of cancer drug development. Mol BioSyst. 2005;1(1):17-26. doi:10.1039/b501751n PMid:16948194
  44. Collins I, Workman P. New approaches to molecular cancer therapeutics. Nat Chem Biol. 2006;2(12):689-700. doi:10.1038/nchembio840 PMid:17108987
  45. Jacobs JJ, Snackey C, Geldof AA, Characiejus D, Van Moorselaar RJA, Den Otter W. Inefficacy of therapeutic cancer vaccines and proposed improvements. Casus of prostate cancer. Anticancer Res. 2014;34(6):2689-700.
  46. Barceloux DG. Selenium. J Toxicol Clin Toxicol. 1999;37(2):145-72. doi:10.1081/CLT-100102417 PMid:10382553
  47. Barclay MN, MacPherson A, Dixon J. Selenium content of a range of UK foods. J Food Compost Anal. 1995;8(4):307-18. doi:10.1006/jfca.1995.1025
  48. Brozmanová J, Mániková D, Vlčková V, Chovanec M. Selenium: a double-edged sword for defense and offence in cancer. Arch Toxicol. 2010;84(12):919-38. doi:10.1007/s00204-010-0595-8 PMid:20871980
  49. Fairweather-Tait SJ, Bao Y, Broadley MR, Collings R, Ford D, Hesketh JE, et al. Selenium in human health and disease. Antioxid Redox Signal. 2011;14(7):1337-83. doi:10.1089/ars.2010.3275 PMid:20812787
  50. Finley JW. Bioavailability of selenium from foods. Nutr rev. 2006; 64 (3):146-51. doi:10.1111/j.1753-4887.2006.tb00198.x PMid:16572602
  51. Sathe SK, Mason AC, Rodibaugh R, Weaver CM. Chemical form of selenium in soybean (Glycine max L.) lectin. J Agric Food Chem. 1992;40(11):2084-91.doi:10.1021/jf00023a010
  52. Navarro-Alarcon M, Lopez-Martinez MC. Essentiality of selenium in the human body: relationship with different diseases. Sci Total Environ. 2000;249(1-3):347-71.doi:10.1016/S0048-9697(99)00526-4
  53. Sirichakwal PP, Puwastien P, Polngam J, Kongkachuichai R. Selenium content of Thai foods. J Food Composit Anal. 2005; 18 (1):47-59.doi:10.1016/j.jfca.2003.10.010
  54. Pappa EC, Pappas AC, Surai PF. Selenium content in selected foods from the Greek market and estimation of the daily intake. Sci Total Environ. 2006; 372 (1): 100-8. doi:10.1016/j.scitotenv.2006.08.008 PMid:16959300
  55. Fisinin VI, Papazyan TT, Surai PF. Producing selenium-enriched eggs and meat to improve the selenium status of the general population. Crit Rev Biotechnol. 2009; 29(1):18-28. doi:10.1080/07388550802658030 PMid:19514900
  56. Davis CD. Selenium supplementation and cancer prevention. Curr Nutr Rep. 2012;1:16-23. doi:1007/s13668-011-0003-x
  57. Dumont E, Vanhaecke F, Cornelis R. Selenium speciation from food source to metabolites: a critical review. Anal Bioanal Chem. 2006;385(7):1304-23. doi:10.1007/s00216-006-0529-8 PMid:16830114
  58. Kápolna E, Fodor P. Bioavailability of selenium from selenium-enriched green onions (Allium fistulosum) and chives (Allium schoenoprasum) after 'in vitro'gastrointestinal digestion. Int J Food Sci Nutr. 2007;58(4):282-96. doi:10.1080/09637480601154335 PMid:17566890
  59. Manjusha R, Dash K, Karunasagar D. UV-photolysis assisted digestion of food samples for the determination of selenium by electrothermal atomic absorption spectrometry (ETAAS). Food Chem. 2007;105(1):260-5.doi:10.1016/j.foodchem.2006.11.011
  60. Wolf WR, Goldschmidt RJ. Updated estimates of the selenomethionine content of NIST wheat reference materials by GC-IDMS. Anal Bioanal Chem. 2007;387(7):2449-52. doi:10.1007/s00216-006-0839-x PMid:17123069
  61. Singh V, Garg A. Availability of essential trace elements in Indian cereals, vegetables and spices using INAA and the contribution of spices to daily dietary intake. Food Chem. 2006;94(1):81-9. doi:10.1016/j.foodchem.2004.10.053
  62. Pérez-Corona M, Sánchez-Martínez M, Valderrama M, Rodríguez M, Cámara C, Madrid Y. Selenium biotransformation by Saccharomyces cerevisiae and Saccharomyces bayanus during white wine manufacture: laboratory-scale experiments. Food Chem. 2011;124(3):1050-5. doi:10.1016/j.foodchem.2010.07.073
  63. Maseko T, Callahan DL, Dunshea FR, Doronila A, Kolev SD, Ng K. Chemical characterisation and speciation of organic selenium in cultivated selenium-enriched Agaricus bisporus. Food Chem. 2013;141(4):3681-7. doi:10.1016/j.foodchem.2013.06.027 PMid:23993536
  64. Deveau M. Contribution of drinking water to dietary requirements of essential metals. J Toxicol Environ health Part A. 2010;73(2):235-41. doi:10.1080/15287390903340880 PMid:20077293
  65. Sager M. Selenium in agriculture, food, and nutrition. Pure Appl Chem. 2006;78(1):111-33.doi:10.1351/pac200678010111
  66. Thomson C, Robinson M. Selenium content of foods consumed in Otago, New Zealand. N Z Med J. 1990;103(886):130-5.
  67. Zhang X, Shi B, Spallholz JE. The selenium content of selected meats, seafoods, and vegetables from Lubbock, Texas. Biol Trace Elem Res. 1993;39(2-3):161-9. doi:10.1007/BF02783186 PMid:7509173
  68. Schomburg L, Schweizer U, Kohrle J. Selenium and selenoproteins in mammals: extraordinary, essential, enigmatic. Cell Mol Life Sci: CMLS. 2004; 61(16):1988-95. doi:10.1007/s00018-004-4114-z PMid:15316649
  69. Tinggi U. Essentiality and toxicity of selenium and its status in Australia: a review. Toxicol Lett. 2003;137(1-2):103-10.doi:10.1016/S0378-4274(02)00384-3
  70. Soda K, Tanaka H, Esaki N. Biochemistry of physiologically active selenium compounds. Organic Selenium and Tellurium Compounds: (1987). 2010:349-65.doi:10.1002/9780470771785.ch7
  71. Selenius M, Fernandes AP, Brodin O, Björnstedt M, Rundlöf A-K. Treatment of lung cancer cells with cytotoxic levels of sodium selenite: effects on the thioredoxin system. Biochem Pharmacol. 2008;75(11):2092-9. doi:10.1016/j.bcp.2008.02.028 PMid:18405881
  72. Xiang N, Zhao R, Zhong W. Sodium selenite induces apoptosis by generation of superoxide via the mitochondrial-dependent pathway in human prostate cancer cells. Cancer Chemother Pharmacol. 2009;63(2):351-62. doi:10.1007/s00280-008-0745-3 PMid:18379781 PMCid:PMC2592502
  73. Fu L, Liu Q, Shen L, Wang Y. Proteomic study on sodium selenite-induced apoptosis of human cervical cancer HeLa cells. J Trace Elem Med Biol. 2011;25(3):130-7. doi:10.1016/j.jtemb.2011.06.001 PMid:21767938
  74. Rigobello MP, Gandin V, Folda A, Rundlöf A-K, Fernandes AP, Bindoli A, et al. Treatment of human cancer cells with selenite or tellurite in combination with auranofin enhances cell death due to redox shift. Free Radic Biol Med. 2009;47(6):710-21. doi:10.1016/j.freeradbiomed.2009.05.027 PMid:19486940
  75. Li Z, Meng J, Xu T, Qin X, Zhou X. Sodium selenite induces apoptosis in colon cancer cells via Bax-dependent mitochondrial pathway. Eur Rev Med Pharmacol Sci. 2013;17(16):2166-71.
  76. Olm E, Jönsson-Videsäter K, Ribera-Cortada I, Fernandes AP, Eriksson LC, Lehmann S, et al. Selenite is a potent cytotoxic agent for human primary AML cells. Cancer Lett. 2009; 282 (1):116-23. doi:10.1016/j.canlet.2009.03.010 PMid:19345479
  77. Philchenkov A, Zavelevich M, Khranovskaya N, Surai P. Comparative analysis of apoptosis induction by selenium compounds in human lymphoblastic leukemia MT-4 cells. Exp Oncol. 2007;29(4):257-61.
  78. Celik HA, Aydin HH, Deveci R, Terzioglu E, Karacali S, Saydam G, et al. Biochemical and morphological characteristics of selenite-induced apoptosis in human hepatoma Hep G2 cells. Biol Trace Elem Res. 2004;99(1-3):27-39.doi:10.1385/BTER:99:1-3:027
  79. Bandura L, Drukala J, Wolnicka-Glubisz A, Björnstedt M, Korohoda W. Differential effects of selenite and selenate on human melanocytes, keratinocytes, and melanoma cells. Biochem Cell Biol. 2005;83(2):196-211. doi:10.1139/o04-130 PMid:15864328
  80. Nilsonne G, Sun X, Nyström C, Rundlöf A-K, Fernandes AP, Björnstedt M, et al. Selenite induces apoptosis in sarcomatoid malignant mesothelioma cells through oxidative stress. Free Radic Biol Med. 2006; 41 (6):874-85. doi:10.1016/j.freeradbiomed.2006.04.031 PMid:16934670
  81. Echigo S, Rikiishi H. Possible role of glutathione in mitochondrial apoptosis of human oral squamous cell carcinoma caused by inorganic selenium compounds. Int J Oncol. 2005;27: 489-95.
  82. Yang JG, Hill KE, Burk RF. Dietary selenium intake controls rat plasma selenoprotein P concentration. J Nutr. 1989;119(7):1010-2. doi:10.1093/jn/119.7.1010 PMid:2754506
  83. Rayman MP. Selenium and human health. Lancet. 2012; 379 (9822):1256-68. doi:10.1016/S0140-6736(11)61452-9
  84. Jackson MI, Combs GF. Selenium and anticarcinogenesis: underlying mechanisms. Curr Opin Clin Nutr Metabol Care. 2008;11(6):718-26. doi:10.1097/MCO.0b013e3283139674 PMid:18827575
  85. Schrauzer GN. Selenomethionine: a review of its nutritional significance, metabolism and toxicity. J Nutr. 2000;130(7):1653-6. doi:10.1093/jn/130.7.1653 PMid:10867031
  86. Davis CD, Tsuji PA, Milner JA. Selenoproteins and cancer prevention. Ann rev Nutr. 2012;32:73-95. doi:10.1146/annurev-nutr-071811-150740 PMid:22404120
  87. Rosen BP, Liu Z. Transport pathways for arsenic and selenium: a minireview. Environ Int. 2009; 35 (3):512-5. doi:10.1016/j.envint.2008.07.023 PMid:18789529 PMCid:PMC2719050
  88. Papp LV, Lu J, Holmgren A, Khanna KK. From selenium to selenoproteins: synthesis, identity, and their role in human health. Antioxid Redox Signal. 2007;9(7):775-806. doi:10.1089/ars.2007.1528 PMid:17508906
  89. Strain J, Bokje E, van't Veer P, Coulter J, Stewart C, Logan H, et al. Thyroid hormones and selenium status in breast cancer. Nutr Cancer. 1997;27(1):48-52. doi:10.1080/01635589709514500 PMid:8970181
  90. Patrick L. Selenium biochemistry and cancer: a review of the literature. Altern Med Rev. 2004;9(3):239-59.
  91. Zhang J, Dong W, Lin J. Reduced selenium-binding protein 1 is associated with poor survival rate in gastric carcinoma. Med Oncol. 2011;28(2):481-7. doi:10.1007/s12032-010-9482-7 PMid:20354826
  92. Van Cauwenbergh R, Robberecht H, Van Vlaslaer V, Deelstra H. Comparison of the serum selenium content of healthy adults living in the Antwerp region (Belgium) with recent literature data. J Trace Elem Med Biol. 2004;18(1):99-112. doi:10.1016/j.jtemb.2004.04.004 PMid:15487770
  93. Li N, Gao Z, Luo D, Tang X, Chen D, Hu Y. Selenium level in the environment and the population of Zhoukoudian area, Beijing, China. Sci Total Environ. 2007; 381 (1): 105-11. doi:10.1016/j.scitotenv.2007.03.027 PMid:17509665
  94. Cabañero AI, Madrid Y, Cámara C. Mercury-selenium species ratio in representative fish samples and their bioaccessibility by an in vitro digestion method. Biol Trace Elem Res. 2007; 119(3):195-211. doi:10.1007/s12011-007-8007-5 PMid:17916943
  95. Gammelgaard B, Rasmussen LH, Gabel-Jensen C, Steffansen B. Estimating intestinal absorption of inorganic and organic selenium compounds by in vitro flux and biotransformation studies in Caco-2 cells and ICP-MS detection. Biol Trace Elem Res. 2012;145(2):248-56. doi:10.1007/s12011-011-9174-y PMid:21863324
  96. Suzuki K, Ogra Y. Metabolic pathway for selenium in the body: speciation by HPLC-ICP MS with enriched Se. Food Addit Contam. 2002;19(10):974-83. doi:10.1080/02652030210153578 PMid:12443560
  97. Suzuki Y, Hashiura Y, Matsumura K, Matsukawa T, Shinohara A, Furuta N. Dynamic pathways of selenium metabolism and excretion in mice under different selenium nutritional statuses. Metallomics. 2010;2(2):126-32. doi:10.1039/B915816B PMid:21069143
  98. Thomson C. Assessment of requirements for selenium and adequacy of selenium status: a review. Eur J Clin Nutr. 2004; 58 (3):391-402. doi:10.1038/sj.ejcn.1601800 PMid:14985676
  99. Allan CB, Lacourciere GM, Stadtman TC. Responsiveness of selenoproteins to dietary selenium 1, 2. Ann Rev Nutr. 1999;19 (1):1-16. doi:10.1146/annurev.nutr.19.1.1 PMid:10448514
  100. Akl MA, Ismael DS, El-Asmy AA. Precipitate flotation-separation, speciation and hydride generation atomic absorption spectrometric determination of selenium (IV) in food stuffs. Microchem J. 2006;83(2):61-9. doi:10.1016/j.microc.2006.02.003
  101. Van Der Torre HW, Van Dokkum W, Schaafsma G, Wedel M, Ockhuizen T. Effect of various levels of selenium in wheat and meat on blood Se status indices and on Se balance in Dutch men. Br J Nutr. 1991; 65 (01): 69-80. doi:10.1079/BJN19910067 PMid:1997131
  102. Fox T, Van den Heuvel E, Atherton C, Dainty J, Lewis D, Langford N, et al. Bioavailability of selenium from fish, yeast and selenate: a comparative study in humans using stable isotopes. Eur J Clin Nutr. 2004; 58 (2): 343-9. doi:10.1038/sj.ejcn.1601787 PMid:14749756
  103. Allowances NRCCoD, Food NRC, Board N. Recommended dietary allowances: National Academies; 1980.
  104. Bendich A. Dietary reference intakes for vitamin C, vitamin E, selenium, and carotenoids institute of medicine washington, DC: National Academy Press, 2000 ISBN: 0-309-06935-1. Nutrition. 2001;17(4):364.doi:10.1016/S0899-9007(00)00596-7
  105. Bitterli C, Bañuelos G, Schulin R. Use of transfer factors to characterize uptake of selenium by plants. J Geochem Explor. 2010;107(2):206-16.doi:10.1016/j.gexplo.2010.09.009
  106. Şlencu BG, Ciobanu C, Cuciureanu R. Selenium content in foodstuffs and its nutritional requirement for humans. Clujul Med. 2014;85(2):139-45.
  107. Rayman MP. Selenium in cancer prevention: a review of the evidence and mechanism of action. Proc Nutr Soc. 2005;64 (04): 527-42. doi:10.1079/PNS2005467 PMid:16313696
  108. Wasowicz W, Gromadzinska J, Rydzynski K, Tomczak J. Selenium status of low-selenium area residents: Polish experience. Toxicol Lett. 2003;137(1):95-101.doi:10.1016/S0378-4274(02)00383-1
  109. Combs GF. Selenium in global food systems. Br J Nutr. 2001;85(05):517-47. doi:10.1079/BJN2000280 PMid:11348568
  110. Schwarz K, Foltz CM. J. Am. Chem. Soc. 1957; 79:3292-3293.doi:10.1021/ja01569a087
  111. Schwarz K, Stesney JA, Foltz C. Relation between selenium traces in L-cystine and protection against dietary liver necrosis. Metabolism. 1959;8:88-90.
  112. Hatfield DL, Tsuji PA, Carlson BA, Gladyshev VN. Selenium and selenocysteine: roles in cancer, health, and development. Trends Biochem Sci. 2014; 39 (3): 112-20. doi:10.1016/j.tibs.2013.12.007 PMid:24485058 PMCid:PMC3943681
  113. Alves MR, Starling AL, Kanufre VC, Soares RD, Norton RdC, Aguiar MJ, et al. Selenium intake and nutritional status of children with phenylketonuria in Minas Gerais, Brazil. J de Pediatria. 2012;88(5):396-400. doi:10.2223/JPED.2217 PMid:23092958
  114. Eroglu C, Unal D, Cetin A, Orhan O, Sivgin S, OZTÜRK A. Effect of serum selenium levels on radiotherapy-related toxicity in patients undergoing radiotherapy for head and neck cancer. Anticancer Res. 2012;32(8):3587-90.
  115. Mistry HD, Pipkin FB, Redman CW, Poston L. Selenium in reproductive health. Am J Obstet Gynecol. 2012;206 (1):21-30. doi:10.1016/j.ajog.2011.07.034 PMid:21963101
  116. Kryczyk J, Zagrodzki P. Selen w chorobie Gravesa-Basedowa. Postepy Hig Med Dosw. 2013;67:491-8. doi:10.5604/17322693.1051000 PMid:23752601
  117. Chen X, Yang G, Chen J, Chen X, Wen Z, Ge K. Studies on the relations of selenium and Keshan disease. Biol Trace Elem Res. 1980;2(2):91-107. doi:10.1007/BF02798589 PMid:24272892
  118. Ge K, Yang G. The epidemiology of selenium deficiency in the etiological study of endemic diseases in China. Am J clin Nutr. 1993;57(2):259S-63S. doi:10.1093/ajcn/57.2.259S PMid:8427200
  119. Zhang S, Rocourt C, Cheng W-H. Selenoproteins and the aging brain. Mech Ageing Dev. 2010; 131 (4):253-60. doi:10.1016/j.mad.2010.02.006 PMid:20219520
  120. Thiry C, Ruttens A, De Temmerman L, Schneider Y-J, Pussemier L. Current knowledge in species-related bioavailability of selenium in food. Food Chem. 2012; 130 (4):767-84.doi:10.1016/j.foodchem.2011.07.102
  121. Fernández-Martínez A, Charlet L. Selenium environmental cycling and bioavailability: a structural chemist point of view. Rev Environ Sci Bio/Technol. 2009;8(1):81-110.doi:10.1007/s11157-009-9145-3
  122. Liu Q, Jiang L, Tian J, Ni J. The molecular biology of selenoproteins and their effects on diseases. Prog Chem. 2009;21: 819-30.
  123. Pedrero Z, Madrid Y. Novel approaches for selenium speciation in foodstuffs and biological specimens: a review. Anal Chim Acta. 2009;634(2):135-52. doi:10.1016/j.aca.2008.12.026 PMid:19185112
  124. Hauksdóttir HL, Webster TJ. Selenium and iron oxide nanocomposites for magnetically-targeted anti-cancer applications. J Biomed Nanotechnol. 2018; 14 (3):510-25. doi:10.1166/jbn.2018.2521 PMid:29663923
  125. Kieliszek M. Selenium-fascinating microelement, properties and sources in food. Molecules. 2019;24(7):1298. doi:10.3390/molecules24071298 PMid:30987088 PMCid:PMC6480557
  126. Thangavel K. Selenium properties for anti-cancer. Res J Pharm Technol. 2017;10(10):3595-7.doi:10.5958/0974-360X.2017.00651.5
  127. Guo CH, Hsia S, Chung CH, Lin YC, Shih MY, Chen PC, et al. Nutritional supplements in combination with chemotherapy or targeted therapy reduces tumor progression in mice bearing triple-negative breast cancer. J Nutr Biochem. 2021; 87:108504. doi:10.1016/j.jnutbio.2020.108504 PMid:32956826
  128. Wu BK, Chen QH, Pan D, Chang B, Sang LX. A novel therapeutic strategy for hepatocellular carcinoma: Immunomodulatory mechanisms of selenium and/or selenoproteins on a shift towards anti-cancer. Int Immunopharmacol. 2021;96: 107790. doi:10.1016/j.intimp.2021.107790 PMid:34162153
  129. Hou Y, Wang W, Bartolo P. A concise review on the role of selenium for bone cancer applications. Bone. 2021:115974. doi:10.1016/j.bone.2021.115974 PMid:33901723
  130. Dhanraj G, Rajeshkumar S. Anticariogenic Effect of Selenium Nanoparticles Synthesized Using Brassica oleracea. J Nanomater. 2021.doi:10.1155/2021/8115585
  131. Kieliszek M. Selenium-fascinating microelement, properties and sources in food. Molecules. 2019(7):1298. doi:10.3390/molecules24071298 PMid:30987088 PMCid:PMC6480557
  132. Ward-Deitrich CL, Whyte E, Hopley C, Rayman MP, Ogra Y, Goenaga-Infante H. Systematic study of the selenium fractionation in human plasma from a cancer prevention trial using HPLC hyphenated to ICP-MS and ESI-MS/MS. Anal Bioanal Chem. 2021;413(2):331-44. doi:10.1007/s00216-020-02988-9 PMid:33140125
  133. Chen N, Zhao C, Zhang T. Selenium transformation and selenium-rich foods. Food Biosci. 2021:100875.doi:10.1016/j.fbio.2020.100875
  134. Dawood MA, Basuini MF, Yilmaz S, Abdel-Latif HM, Kari ZA, Abdul Razab MK, et al. Selenium nanoparticles as a natural antioxidant and metabolic regulator in aquaculture: a review. Antioxidants. 2021;10(9):1364. doi:10.3390/antiox10091364 PMid:34572996 PMCid:PMC8471321
  135. Elfakharany WA, Safwat MM, Essawy AS. Possible protective and curative effects of selenium nanoparticles on testosterone-induced benign prostatic hyperplasia rat model. Folia Morphol. 2021. doi:10.5603/FM.a2021.0113 PMid:34730228
  136. Nayak V, Singh KR, Singh AK, Singh RP. Potentialities of selenium nanoparticles in biomedical science. N J Chem. 2021; 45(6):2849-78.doi:10.1039/D0NJ05884J
  137. Szwiec M, Marciniak W, Derkacz R, Huzarski T, Gronwald J, Cybulski C, et al. Serum Selenium Level Predicts 10-Year Survival after Breast Cancer. Nutrients. 2021;13(3):953. doi:10.3390/nu13030953 PMid:33809461 PMCid:PMC7998294
  138. Rodríguez-Molinero J, Migueláñez-Medrán BD, Puente-Gutiérrez C, Delgado-Somolinos E, Martín Carreras-Presas C, Fernández-Farhall J, et al. Association between Oral Cancer and Diet: An Update. Nutrients. 2021;13(4):1299. doi:10.3390/nu13041299 PMid:33920788 PMCid:PMC8071138
  139. Ruseva B, Himcheva I, Nankova D. Importance of selenoproteins for the function of the thyroid gland. Medicine. 2013;3(1).
  140. Duffield-Lillico AJ, Slate EH, Reid ME, Turnbull BW, Wilkins PA, Combs GF, et al. Selenium supplementation and secondary prevention of nonmelanoma skin cancer in a randomized trial. J Natl Cancer Inst. 2003; 95(19):1477-81. doi:10.1093/jnci/djg061 PMid:14519754
  141. Lacour M, Zunder T, Restle A, Schwarzer G. No evidence for an impact of selenium supplementation on environment associated health disorders-a systematic review. Int J Hyg Environ Health. 2004;207(1):1-13. doi:10.1078/1438-4639-00254 PMid:14762969
  142. Bleys J, Miller ER, Pastor-Barriuso R, Appel LJ, Guallar E. Vitamin-mineral supplementation and the progression of atherosclerosis: a meta-analysis of randomized controlled trials. Am J Clin Nutr. 2006;84(4):880-7. doi:10.1093/ajcn/84.4.880 PMid:17023716
  143. Flores-Mateo G, Navas-Acien A, Pastor-Barriuso R, Guallar E. Selenium and coronary heart disease: a meta-analysis. Am J Clin Nutr. 2006;84(4):762-73. doi:10.1093/ajcn/84.4.762 PMid:17023702 PMCid:PMC1829306
  144. You W-c, Brown LM, Zhang L, Li J-y, Jin M-l, Chang Y-s, et al. Randomized double-blind factorial trial of three treatments to reduce the prevalence of precancerous gastric lesions. J Natl Cancer Inst. 2006; 98 (14):974-83. doi:10.1093/jnci/djj264 PMid:16849680
  145. Canter P, Wider B, Ernst E. The antioxidant vitamins A, C, E and selenium in the treatment of arthritis: a systematic review of randomized clinical trials. Rheumatology. 2007;46(8):1223-33. doi:10.1093/rheumatology/kem116 PMid:17522095
  146. Stewart S, Prince M, Bassendine M, Hudson M, James O, Jones D, et al. A randomized trial of antioxidant therapy alone or with corticosteroids in acute alcoholic hepatitis. J Hepatol. 2007; 47(2): 277-83. doi:10.1016/j.jhep.2007.03.027 PMid:17532088
  147. Navarro-Alarcon M, de la Serrana HL-G, Perez-Valero V, López-Martı́nez M. Selenium concentrations in serum of individuals with liver diseases (cirrhosis or hepatitis): relationship with some nutritional and biochemical markers. Sci Total Environ. 2002; 291(1):135-41.doi:10.1016/S0048-9697(01)01088-9
  148. Hanna C, Ścibior D, Skrzycki M, Podsiad M. Glutathione and GSH-dependent enzymes in patients with liver cirrhosis and hepatocellular carcinoma. Acta Biochim Pol. 2006.
  149. Combs Jr F. Biomarkers of selenium status. Nutrients. 2015; 7 (4): 2209-36. doi:10.3390/nu7042209 PMid:25835046 PMCid:PMC4425141
  150. Venardos KM, Kaye DM. Myocardial ischemia-reperfusion injury, antioxidant enzyme systems, and selenium: a review. Curr Med Chem. 2007;14(14):1539-49. doi:10.2174/092986707780831078 PMid:17584062
  151. Geoghegan M, McAuley D, Eaton S, Powell-Tuck J. Selenium in critical illness. Curr Opin Crit Care. 2006;12(2):136-41. doi:10.1097/01.ccx.0000216581.80051.d6 PMid:16543790
  152. Drutel A, Archambeaud F, Caron P. Selenium and the thyroid gland: more good news for clinicians. Clin Endocrinol. 2013; 78 (2):155-64. doi:10.1111/cen.12066 PMid:23046013
  153. Kamwesiga J, Mutabazi V, Kayumba J, Tayari J-CK, Uwimbabazi JC, Batanage G, et al. Effect of selenium supplementation on CD4+ T-cell recovery, viral suppression and morbidity of HIV-infected patients in Rwanda: a randomized controlled trial. AIDS (London, England). 2015;29(9):1045. doi:10.1097/QAD.0000000000000673 PMid:25870994 PMCid:PMC4444428
  154. Ximena B, Maria Jose M-B, Kathryn M, Guoyan Z, Allan R, Phillip R, et al. Impact of a selenium chemoprevention clinical trial on hospital admissions of HIV-infected participants. HIV Clin Trials. 2002;3(6):483-91. doi:10.1310/A7LC-7C9V-EWKF-2Y0H PMid:12501132
  155. Rayman MP. The importance of selenium to human health. Lancet. 2000;356(9225):233-41.doi:10.1016/S0140-6736(00)02490-9
  156. Chen J, Berry MJ. Selenium and selenoproteins in the brain and brain diseases. J Neurochem. 2003;86(1):1-12. doi:10.1046/j.1471-4159.2003.01854.x PMid:12807419
  157. de Jong N, Gibson RS, Thomson CD, Ferguson EL, McKenzie JE, Green TJ, et al. Selenium and zinc status are suboptimal in a sample of older New Zealand women in a community-based study. J Nutr. 2001;131(10):2677-84. doi:10.1093/jn/131.10.2677 PMid:11584090
  158. Pieczyńska J, Grajeta H. The role of selenium in human conception and pregnancy. J Trace Elem Med Biol. 2015;29:31-8. doi:10.1016/j.jtemb.2014.07.003 PMid:25175508
  159. Faure P, Ramon O, Favier A, Halimi S. Selenium supplementation decreases nuclear factor‐kappa B activity in peripheral blood mononuclear cells from type 2 diabetic patients. Eur J Clin Investig. 2004; 34 (7): 475-81. doi:10.1111/j.1365-2362.2004.01362.x PMid:15255784