Abstract
It has been 50 years since the surprising discovery in 1949 that selenium (Se) had cancer preventing properties in animals given a chemical carcinogen (1). Numerous studies have confirmed the anticarcinogenic effects of supranutritional levels of Se in animals and more recently in humans given supplemental Se, as described by Combs (2). Proposed mechanisms of action for Se, as reviewed elsewhere in more detail (3), are based on (i) the formation of selenoproteins and (ii) the generation of low molecular weight Se metabolites by intermediary metabolism of Se in animals. A collaborative project (4,5) to investigate mechanisms and develop improved forms of Se for cancer prevention has provided considerable evidence that methylated metabolites of Se are important for Se anticarcinogenic action in animal model systems. The objective of this article is to summarize the findings that led to this concept and describe applications using methylated selenoamino acids that occur naturally in plants as a practical delivery mechanism for chemoprevention.
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References
Clayton, C.C., and Baumann, C.A. (1949) Diet and azo dye tumors: Effect of diet during period when the dye is not fed. Cancer Res. 9, 575–592.
Combs, G. F., Jr. Considering the mechanisms of cancer prevention by selenium. InNutrition and Cancer Prevention: New Insights Into the Role of Phytochemicals. Kluwer Academic/Plenum, New York, 2000 [This volume].
Ganther, H. E. (1999) Selenium metabolism, selenoproteins, and mechanisms of cancer prevention: Complexities with thiorcdoxin reductase. Carcinogenesis 20, 1657–1666.
Ip, C. (1998) Lessons from basic research in selenium and cancer prevention. J. Nutr. 128, 1845–1854.
Ganther, H.E., and Lawrence, J.R. (1997) Chemical transformations of selenium in living organisms. Improved forms of selenium for cancer prevention. Tetrahedron 53, 12229–12310.
Hoffmeister, F. (1894) Ueber Methylirung im Thierkörper. Arch. Exp. Path. Pharmacol. 33, 198–215.
Andreadou, I, Water, B, Commandeur, J.N.M., Worthington, E.A, and Vermeulen, N.P.E. (1996) Comparative cytotoxicity of 14 novel selenocysteine Se-conjugates in rat renal proximal tubular cells. Toxicol. Appl. Pharmacol. 141, 278–287.
Uden, P. C., Bird, S. M., Kotrebai, M., Nolibos, P., Tyson, J. F., Block, E., and Denoyer, E. (1998) Analytical selenoaminoacid studies by chromatography with interfaced atomic mass spectrometry and atomic emission spectral detection. Fresenius J. Anal. Chem. 362, 447–456.
Hsieh, H. S., and Ganther, H. E. (1977) Biosynthesis of dimethyl selenide from sodium selenite in rat liver and kidney cell-free systems. Biochim. Biophys. Acta 497,205–217.
Mozier, N. M., McConnell, K. P., and Hoffman, J. L. (1988) S-adenosyl-Lmethionine:thioether S-methyltransferase, a new enzyme in sulfur and selenium metabolism. J. Biol. Chem. 263, 4527–4531.
Vadhanavikit, S., Ip, C., and Ganther, H. E. (1993) Metabolites of sodium selenite and methylated selenium compounds administered at cancer chemopreventive levels in the rat. Xenobiotica 23, 731–745.
Ip, C., and Ganther, H. E. Novel strategies in selenium cancer chemoprevention research. In Selenium in Biology and Health Burk, R., ed., Springer-Verlag, Berlin, 1994.
Spallholz, J. E. (1994) On the nature of selenium toxicity and carcinostatic activity. Free Radical Biol. & Med. 17, 45–64.
Ip, C., and Ganther, H. E. Relationship between the chemical form of selenium and anticarcinogenic activity. In Cancer Chemoprevention. Wattenberg, L, Lipkin, M, Boone, C. W., and Kelloff, G, J., eds., CRC Press, Boca Raton, 1992.
Ip, C., Lisk, D. J., and Ganther, H. E. (1998) Activities of structurally-related lipophilic selenium compounds as cancer chemopreventive agents. Anticancer Res. 18, 4019–4026.
Ip, C., Hayes, C., Budnick, R. M., and Ganther, H. E. (1991) Chemical form of selenium, critical metabolites, and cancer prevention. Cancer Res. 51, 595–600.
Weinshilboum, R. M., Otterness, D. M., and Szumlanski, C. L. (1999) Methylation pharmacogenetics: Catechol 0-methyltransferase, thiopurine methyltransferase, and histamine N-methyltransferase. Annu. Rev. Pharmacol. Toxicol. 39, 19–52.
Trelease, S. F., Di Somma, A. A., and Jacobs, A. L. (1960) Seleno-amino acid found in Astragalus bisulcatus. Science 132, 618.
Neuhierl, B., Thanbichler, M., Lottspeich, F., and Bock, A. (1999) A family of Smethylmethionine-dependent thiol/selenol methyltransferases. J. Biol. Chem. 274, 5407–5414.
Foster, S. J., Kraus, R.J., and Ganther, H. E. (1986) The metabolism of selenomethionine, Se-methylselenocysteine, their selenonium derivatives, and trimethylselenonium in the rat. Arch. Biochem. Biophys. 251, 77–86.
Andreadou, I, Menge, W. M. P. B., Commandeur, J.N.M., Worthington, E.A, and Vermeulen, N.P.E. (1996) Synthesis of novel Se-substituted selenocysteine derivatives as potential kidney selective prodrugs of biologically active selenol compounds: Evaluation of kinetics of 13-elimination reactions in rat renal cytosol. J. Med. Chem. 39, 2040–2046.
Ip, C., Zhu, Z., Thompson, H. J., Lisk, D., and Ganther, H. E. (1999) Chemoprevention of mammary cancer with Se-allylselenocysteine and other selenoamino acids in the rat. Anticancer Res., 19 (in press)
Ip, C, and Lisk, D. J. (1996) The attributes of selenium-enriched garlic in cancer prevention. Adv. Exp. Med. Biol. 401, 179–187.
Lu, J., Pei, H., Ip, C., Lisk, D. J., Ganther, H., and Thompson, H. J. (1996) Effect of an aqueous extract of selenium-enriched garlic on in vitro markers and in vivo efficacy in cancer prevention. Carcinogenesis 17, 1903–1907.
Ip, C., Birringer, M., Block, E., Kotrebai, M., Tyson, J. F., Uden, P. C., and Lisk, D. J. Chemical speciation influences comparative activity of selenium-enriched garlic and yeast in mammary cancer prevention. (submitted)
Medina, D., and Morrison, D.G. (1988) Current ideas on selenium as a chemopreventive agent. Pathol. Immunopathol. Res. 7,187–199.
Wilson, A.C., Thompson, H.J., Schedin, P.J., Gibson, N.W., and Ganther, H.E. (1992) Effect of methylated forms of selenium on cell viability and the induction of DNA strand breakage. Biochem. Pharmacol. 43, 1137–1141.
Lu, J. Apoptosis and angiogenesis in cancer prevention by selenium. InNutrition and Cancer Prevention: New Insights into the Role of Phytochemicals. Kluwer Academic/Plenum, New York, 2000. [This volume]
Sinha, R, and Medina, D. (1997) Inhibition of cdk2 kinase activity by methylselenocysteine in synchronized mouse mammary epithelial tumor cells. Carcinogenesis 18, 1541–1547.
Sinha, R., Ganther, H. E., and Medina, D. (1999) Methylseleninic acid, a novel selenium compound inhibits mouse mammary epithelial tumor cells in vitro. Proc. Amer. Assoc. Cancer Res. 40, 360.
Gopalakrishna, R., Gundimeda, U., and Chen, S.-H. (1997) Cancer-preventive selenocompounds induce a specific redox modification of cysteine-rich regions in Ca2+-dependent isozymes of protein kinase C. Arch. Biochem. Biophys. 348, 25–36.
Simons, S. S., Jr., and Pratt, W. B. (1995) Glucocorticoid receptor thiols and steroid-binding activity. Methods Enzymoll. 251, 406–422.
Jacob, C., Maret, W., and Vallee, B. L. (1999) Selenium redox biochemistry of zinc-sulfur coordination sites in proteins and enzymes. Proc. Nat. Acad. Sci. (U. S.) 96, 1910–1914.
Foster, S. J., Kraus, R. J., and Ganther, H. E. (1986) Formation of dimethyl selenide and trimethylselenonium from selenobetaine in the rat. Arch. Biochem. Biophys. 247,12–19.
Ip, C., and Ganther, H. E. (1990) Activity of methylated forms of selenium in cancer prevention. Cancer Res. 50, 1206–1211.
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Ganther, H.E. (2001). Selenium Metabolism and Mechanisms of Cancer Prevention. In: Nutrition and Cancer Prevention. Advances in Experimental Medicine and Biology, vol 492. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1283-7_10
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DOI: https://doi.org/10.1007/978-1-4615-1283-7_10
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