Selenium and Cancer: from Prevention to Treatment

Authors: J. Brozmanová
Authors‘ workplace: Laboratórium molekulárnej genetiky, Ústav experimentálnej onkológie SAV, Bratislava, Slovenská republika
Published in: Klin Onkol 2011; 24(3): 171-179
Category: Reviews


Selenium (Se) is an essential dietary component for all animals, including human beings, that is regarded as a protective agent against cancer. Although the mode of its anticancer action is not yet fully understood, several mechanisms, such as antioxidant protection through selenoenzymes, stimulation of DNA repair, and apoptosis in tumor prestages have all been proposed. Despite the unsupported results of the last ”SELECT“ trial, the cancer-preventing activity of Se has been demonstrated in a majority of epidemiological studies. Moreover, recent studies suggest that Se has a potential to be used not only in cancer prevention but also in cancer treatment, where in combination with other anticancer drugs or radiation it may increase the efficacy of cancer therapy. In combating cancer cells, Se acts as a prooxidant rather than an antioxidant, inducing apoptosis through the generation of oxidative stress. Thus, inorganic Se compounds, having high redox potency, represent a promising option in cancer therapy.

Key words:
selenium – cancer prevention – selenoproteins – cancer treatment – oxidative stress

This study was supported by the VEGA grant agency of the Slovak Republic (No. 2/6082/26).

The author declares she has no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.


1. Rayman MP. The importance of selenium to human health. Lancet 2000; 356(9225): 233–241.

2. Stranges S, Marshall JR, Natarajan R et al. Effects of long-term selenium supplementation on the incidence of type 2 diabetes: a randomized trial. Ann Intern Med 2007; 147(4): 217–223.

3. Laclaustra M, Navas-Acien A, Stranges S et al. Serum selenium concentrations and diabetes in U.S. adults: National Health and Nutrition Examination Survey (NHANES) 2003–2004. Environ Health Perspect 2009; 117(9): 1409–1413.

4. Oldfield JE. The two faces of selenium. J Nutr 1987; 117(12): 2002–2008.

5. Schwarz K, Foltz CM. Selenium as an integral part of factor 3 against dietary necrotic liver degeneration. J Am Chem Soc 1957; 79(12): 3292–3293.

6. Shamberger RJ, Frost DV. Possible protective effect of selenium against human cancer. Can Med.Assoc J 1969; 100(14): 682.

7. Schrauzer GN, White DA, Schneider CJ. Cancer mortality correlation studies III: statistical associations with die­tary selenium intakes. Bioinorg Chem 1977; 7(1): 23–31.

8. Schrauzer GN, White DA, Schneider CJ. Cancer mortality correlation studies IV: associations with dietary intakes and blood levels of certain trace elements, notably Se-antagonists. Bioinorg Chem 1977; 7(1): 35–56.

9. Combs GF Jr, Gray WP. Chemopreventive agents: selenium. Pharmacol Ther 1998; 79(3): 179–192.

10. Whanger PD. Selenium and its relationship to cancer: an update. Br J Nutr 2004; 91(1): 11–28.

11. Yu SY, Zhu YJ, Li WG. Protective role of selenium against hepatitis B virus and primary liver cancer in Qidong. Biol Trace Elem Res 1997; 56(1): 117–124.

12. Wei WQ, Abnet CC, Qiao YL et al. Prospective study of serum selenium concentrations and esophageal and gastric cardia cancer, heart disease, stroke, and total death. Am J Clin Nutr 2004; 79(1): 80–85.

13. Clark LC, Combs GF Jr, Turnbull BW 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(24): 1957–1963.

14. Klein EA, Thompson IM, Lippman SM et al. SELECT: the Selenium and Vitamin E Cancer Prevention Trial: rationale and design. Prostate Cancer Prostatic Dis 2000; 3(3): 145–151.

15. Lippman SM, Klein EA, Goodman PJ et al. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 2009; 301(1): 39–51.

16. Rayman MP, Combs GF Jr, Waters DJ. Selenium and vitamin E supplementation for cancer prevention. JAMA 2009; 301(18): 1876.

17. Platz EA, Lippman SM. Selenium, genetic variation, and prostate cancer risk: epidemiology reflects back on selenium and vitamin E cancer prevention trial. J Clin Oncol 2009; 27(22): 3569–3572.

18. Valko M, Leibfritz D, Moncol J et al. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 2007; 39(1): 44–84.

19. Rayman MP. Selenoproteins and human health: insights from epidemiological data. Biochim Biophys Acta 2009; 1790(11): 1533–1540.

20. Björkhem-Bergman L, Torndal UB, Eken S et al. Selenium prevents tumor development in a rat model for chemical carcinogenesis. Carcinogenesis 2005; 26(1): 125–131.

21. Seo YR, Kelley MR, Smith ML. Selenomethionine regulation of p53 by a ref1-dependent redox mechanism. Proc Natl Acad Sci USA 2002; 99(22): 14548–4553.

22. Gopee NV, Johnson VJ, Sharma RP. Sodium selenite-induced apoptosis in murine B-lymphoma cells is associated with inhibition of protein kinase C-delta, nuclear factor kappaB, and inhibitor of apoptosis protein. Toxicol Sci 2004; 78(2): 204–214.

23. el-Bayoumy K, Chae YH, Upadhyaya P et al. Inhibition of 7,12-dimethylbenz(a)anthracene-induced tumors and DNA adduct formation in the mammary glands of female Sprague-Dawley rats by the synthetic organoselenium compound, 1,4-phenylenebis(methylene)selenocyanate. Cancer Res 1992; 52(9): 2402–2407.

24. Pagmantidis V, Méplan C, van Schothorst EM et al. Supplementation of healthy volunteers with nutritionally relevant amounts of selenium increases the expression of lymphocyte protein biosynthesis genes. Am J Clin Nutr 2008; 87(1): 181–189.

25. Ravn-Haren G, Krath BN, Overvad K et al. Effect of long-term selenium yeast intervention on activity and gene expression of antioxidant and xenobiotic metabolising enzymes in healthy elderly volunteers from the Danish Prevention of Cancer by Intervention by Selenium (PRECISE) pilot study. Br J Nutr 2008; 99(6): 1190–1198.

26. Narayanan BA. Chemopreventive agents alters global gene expression pattern: predicting their mode of action and targets. Curr Cancer Drug Targets 2006; 6(8): 711–727.

27. Spallholz JE, Palace VP, Reid TW. Methioninase and selenomethionine but not Se-methylselenocysteine generate methylselenol and superoxide in an in vitro chemiluminescent assay: implications for the nutritional carcinostatic activity of selenoamino acids. Biochem Pharmacol 2004; 67(3): 547–554.

28. Szatrowski TP, Nathan CF. Production of large amounts of hydrogen peroxide by human tumor cells. Cancer Res 1991; 51(3): 794–798.

29. Kong Q, Beel JA, Lillehei KO. A threshold concept for cancer therapy. Med Hypotheses 2000; 55(1): 29–35.

30. Trachootham D, Zhou Y, Zhang H et al. Selective killing of oncogenically transformed cells through a ROS-mediated mechanism by beta-phenylethyl isothiocyanate. Cancer Cell 2006; 10(3): 241–252.

31. Trachootham D, Alexandre J, Huang P. Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nat Rev Drug Discov 2009; 8(7): 579–591.

32. Pan JS, Hong MZ, Ren JL. Reactive oxygen species: a double-edged sword in oncogenesis. World J Gastroenterol 2009; 15(14): 1702–1707.

33. Hail N Jr, Cortes M, Drake EN et al. Cancer chemoprevention: a radical perspective. Free Radic Biol Med 2008; 45(2): 97–110.

34. Trachootham D, Lu W, Ogasawara MA et al. Redox regulation of cell survival. Antioxid Redox Signal 2008; 10(8): 1343–1374.

35. Drake EN. Cancer chemoprevention: selenium as a prooxidant, not an antioxidant. Med Hypotheses 2006; 67(2): 318–322.

36. Lipinski B. Rationale for the treatment of cancer with sodium selenite. Med Hypotheses 2005; 64(4): 806–810.

37. Olm E, Fernandes AP, Hebert C et al. Extracellular thiol-assisted selenium uptake dependent on the x(c)- cystine transporter explains the cancer-specific cytotoxicity of selenite. Proc Natl Acad Sci USA 2009; 106(27): 11400–11405.

38. Huang F, Nie C, Yang Y et al. Selenite induces redox­-dependent Bax activation and apoptosis in colorectal cancer cells. Free Radic Biol Med 2009; 46(8): 1186–1196.

39. Menter DG, Sabichi AL, Lippman SM. Selenium effects on prostate cell growth. Cancer Epidemiol Biomarkers Prev 2000; 9(11): 1171–1182.

40. Ghosh J. Rapid induction of apoptosis in prostate cancer cells by selenium: reversal by metabolites of arachidonate 5-lipoxygenase. Biochem Biophys Res Commun 2004; 315(3): 624–635.

41. Bhattacharyya RS, Husbeck B, Feldman D et al. Selenite treatment inhibits LAPC-4 tumor growth and prostate-Specific antigen secretion in a xenograft model of human prostate cancer. Int J Radiat Oncol Biol Phys 2008; 72(3): 935–940.

42. Husbeck B, Bhattacharyya RS, Feldman D et al. Inhibition of androgen receptor signaling by selenite and methylseleninic acid in prostate cancer cells: two distinct mechanisms of action. Mol Cancer Ther 2006; 5(8): 2078–2085.

43. Husbeck B, Nonn L, Peehl DM et al. Tumor-selective killing by selenite in patient-matched pairs of normal and malignant prostate cells. Prostate 2006; 66(2): 218–225.

44. Nilsonne G, Sun X, Nyström C et al. Selenite induces apoptosis in sarcomatoid malignant mesothelioma cells through oxidative stress. Free Radic Biol Med 2006; 41(6):874–885.

45. Selenius M, Rundlöf AK, Olm E et al. Selenium and the selenoprotein thioredoxin reductase in the prevention, treatment and diagnostics of cancer. Antioxid Redox Signal 2010; 12(7): 867–880.

46. Selenius M, Fernandes AP, Brodin O et al. Treatment of lung cancer cells with cytotoxic levels of sodium selenite: effects on the thioredoxin system. Biochem Pharmacol 2008; 75(11): 2092–2099.

47. Kim EH, Sohn S, Kwon HJ et al. Sodium selenite induces superoxide-mediated mitochondrial damage and subsequent autophagic cell death in malignant glioma cells. Cancer Res 2007; 67(13): 6314–6324.

48. Olm E, Jönsson-Videsäter K, Ribera-Cortada I et al. Selenite is a potent cytotoxic agent for human primary AML cells. Cancer Lett 2009; 282(1): 116–123.

49. Vadgama JV, Wu Y, Shen D et al. Effect of selenium in combination with Adriamycin or Taxol on several different cancer cells. Anticancer Res 2000; 20(3A): 1391–1414.

50. Rudolf E, Radocha J, Cervinka M et al. Combined effect of sodium selenite and campthotecin on cervical carcinoma cells. Neoplasma 2004; 51(2): 127–135.

51. Jüliger S, Goenaga-Infante H, Lister TA et al. Chemosensitization of B-cell lymphomas by methylseleninic acid involves nuclear factor-kappaB inhibition and the rapid generation of other selenium species. Cancer Res 2007; 67(22): 10984–10992.

52. Thant AA, Wu Y, Lee J et al. Role of caspases in 5-FU and selenium-induced growth inhibition of colorectal cancer cells. Anticancer Res 2008; 28(6A): 3579–3592.

53. Husbeck B, Peehl DM, Knox SJ. Redox modulation of human prostate carcinoma cells by selenite increases radiation-induced cell killing. Free Radic Biol Med 2005; 38(1): 50–57.

54. Shin SH, Yoon MJ, Kim M et al. Enhanced lung cancer cell killing by the combination of selenium and ionizing radiation. Oncol Rep 2007; 17(1): 209–216.

55. Dennert G, Horneber M. Selenium for alleviating the side effects of chemotherapy, radiotherapy and surgery in cancer patients. Cochrane Database Syst Rev 2006; 3: CD005037.

56. Micke O, Schomburg L, Buentzel J et al. Selenium in oncology: from chemistry to clinics. Molecules 2009; 14(10): 3975–3988.

57. Kiremidjian-Schumacher L, Roy M, Glickman R et al. Selenium and immunocompetence in patients with head and neck cancer. Biol Trace Elem Res 2000; 73(2): 97–111.

58. Federico A, Iodice P, Federico P et al. Effects of selenium and zinc supplementation on nutritional status in patients with cancer of digestive tract. Eur J Clin Nutr 2001; 55(4): 293–297.

59. Sieja K, Talerczyk M. Selenium as an element in the treatment of ovarian cancer in women receiving chemotherapy. Gynecol Oncol 2004; 93(2): 320–327.

60. Asfour IA, El-Tehewi MM, Ahmed MH et al. High-dose sodium selenite can induce apoptosis of lymphoma cells in adult patients with non-Hodgkin’s lymphoma. Biol Trace Elem Res 2008; 127(3): 200–210.

61. Micke O, Bruns F, Mücke R et al. Selenium in the treatment of radiation-associated secondary lymphedema. Int J Radiat Oncol Biol Phys 2003; 56(1): 40–49.

62. Greenlee H, Gammon MD, Abrahamson PE et al. Prevalence and predictors of antioxidant supplement use during breast cancer treatment: the Long Island Breast Cancer Study Project. Cancer 2009; 115(14): 3271–3282.

63. Tabassum A, Bristow RG, Venkateswaran V. Ingestion of selenium and other antioxidants during prostate cancer radiotherapy: a good thing? Cancer Treat Rev 2010; 36(3): 230–234.

64. Manzanares W, Hardy G. Selenium supplementation in the critically ill: posology and pharmacokinetics. Curr Opin Clin Nutr Metab Care 2009; 12(3): 273–280.

65. Vincent JL, Forceville X. Critically elucidating the role of selenium. Curr Opin Anaesthesiol 2008; 21(2): 148–154.

66. Letavayova L, Vlckova V, Brozmanova J. Selenium: from cancer prevention to DNA damage. Toxicology 2006; 227(1–2): 1–14.

67. Overall evaluations of carcinogenicity: an updating of IARC Monographs volumes 1 to 42. IARC Monogr Eval Carcinog Risks Hum Suppl 1987; 7: 1–440.

68. Biswas S, Talukder G, Sharma A. Chromosome damage induced by selenium salts in human peripheral lymphocytes. Toxicol In Vitro 2000; 14(5): 405–408.

69. Letavayova L, Vlasakova D, Spallholz JE et al. Toxicity and mutagenicity of selenium compounds in Saccharomyces cerevisiae. Mutat Res 2008; 638(1–2): 1–10.

70. Wycherly BJ, Moak MA, Christensen MJ. High dietary intake of sodium selenite induces oxidative DNA damage in rat liver. Nutr Cancer 2004; 48(1): 78–83.

71. Brozmanova J, Manikova D, Vlckova V et al Selenium: a double-edged sword for defense and offence in cancer. Arch Toxicol 2010; 84(12): 919–938.

72. Novotny L, Rauko P, Kombian SB et al. Selenium as a chemoprotective anti-cancer agent: reality or wishful thinking? Neoplasma 2010; 57(5): 383–391.

73. Whanger PD. Selenocompounds in plants and animals and their biological significance. J Am Coll Nutr 2002; 21(3): 223–232.

75. Połatajko A, Banaś B, Encinar JR et al. Investigation of the recovery of selenomethionine from selenized yeast by two-dimensional LC-ICP MS. Anal Bioanal Chem 2005; 381(4): 844–849.

Paediatric clinical oncology Surgery Clinical oncology
Forgotten password

Don‘t have an account?  Create new account

Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.


Don‘t have an account?  Create new account