Abstract
This article highlights some recent advances in selenium cancer chemoprevention research. It has been well documented that the chemical transformation of selenium to a monomethylated metabolite is an important step in achieving cancer prevention. Studies with the rat mammary carcinogenesis model suggested that methylselenocysteine (MSC), a good precursor for generating methylselenol endogenously, is able to block clonal expansion of premalignant lesions in the mammary gland. This finding supports the notion that selenium intervenes at an early stage of carcinogenesis. In addition to decreasing cell proliferation of the transformed colonies in vivo, MSC also enhances apoptosis. These same cellular responses are replicated with human premalignant breast cells grown in culture. cDNA microarray analysis indicated that selenium affects a multitude of molecular targets. Based on this information, a number of signaling pathways are proposed that could potentially provide insight into how selenium might block cell cycle progression and induce cell death.
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Clark LC, Combs GF, Turnbull BW, Slate EH, Chalker DK, Chow J, Davis LS, Glover RA, Graham GF, Gross EG, Krongrad A, Lesher JL, Park K, Sanders BB, Smith CL, Taylor R: Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin: A randomized controlled trial. J Am Med Assoc 276: 1957–1985, 1996
Ip C, Hayes C, Budnick RM, Ganther HE: Chemical form of selenium, critical metabolites, and cancer prevention. Cancer Res 51: 595–600, 1991
Medina D, Thompson H, Ganther H, Ip C: Se-Methylselenocysteine: A new compound for chemoprevention of breast cancer. Nutr Cancer 40: 12–17, 2001
Ip C, Ganther HE: Relationship between the chemical form of selenium and anticarcinogenic activity. In: Wattenberg L, Lipkin M, Boone CW, Kelloff GJ (eds) Cancer Chemoprevention, CRC Press, Boca Raton, FL, 1992, pp 479–488
Ip C: Lessons from basic research in selenium and cancer prevention. J Nutr 128: 1845–1854, 1998
Ganther HE, Lawrence JR: Chemical transformations of selenium in living organisms. Improved forms of selenium for cancer prevention. Tetrahedron 53: 12299–12310, 1997
Andreadou I, Menge WMPB, Commandeur JNM, Worthington EA, Vermeulen NPE: Synthesis of novel Se-substituted selenocysteine derivatives as potential kidney selective prodrugs of biologically active selenol compounds: Evaluation of kinetics of β-elimination reactions in rat renal cytosol. J Med Chem 39: 2040–2046, 1996
Ip C, Zhu Z, Thompson HJ, Lisk D, Ganther HE: Chemoprevention of mammary cancer with Se-allylselenocysteine and other selenoamino acids in the rat. Anticancer Res 19: 2875–2880, 1999
Weinshilboum RM, Otterness DM, Szumlanski CL: Methylation pharmacogenetics: Catechol O-methyltransferase, thiopurine methyltransferase, and histamine N-methyltransferase. Annu Rev Pharmacol Toxicol 39: 19–52, 1999
Sunde R: Molecular biology of selenoproteins. Ann Rev Nutr 10: 451–474, 1990
Ip C, Birringer M, Block E, Kotrebai M, Tyson JF, Uden PC, Lisk DJ: Chemical speciation influences comparative activity of selenium-enriched garlic and yeast inmammarycancer prevention. J Agr Food Chem 48: 2062–2070, 2000
Vadhanavikit S, Ip C, Ganther HE: Metabolites of sodium selenite and methylated selenium compounds administered at cancer chemoprevention levels in the rat. Xenobiotica 23: 731–745, 1993
Ip C, Lisk DJ: Bioavailability of selenium from selenium-enriched garlic. Nutr Cancer 20: 129–137, 1993
Ganther HE, Ip C: Thioredoxin reductase activity in rat liver is not affected by supranutritional levels of monomethylated selenium in vivo and is inhibited only by high levels of selenium in vitro. J Nutr 131: 301–304, 2001
Ganther HE: Selenium metabolism, selenoproteins and mechanisms of cancer prevention: complexities with thioredoxin reductase. Carcinogenesis 20: 1657–1666, 1999
Russo J, Tay LK, Russo IH: Differentiation of the mammary gland and susceptibility to carcinogenesis. Breast Cancer Res Treat 2: 5–73, 1982
Ip C, Thompson HJ, Ganther HE: Selenium modulation of cell proliferation and cell cycle biomarkers in normal and premalignant cells of the rat mammary gland. Cancer Epidemiol Biomarkers Prev 9: 49–54, 2000
Ip C, Dong Y: Methylselenocysteine modulates proliferation and apoptosis biomarkers in premalignant lesions of the rat mammary gland. Anticancer Res 21: 863–868, 2001
Ip C, Thompson HJ, Zhu Z, Ganther HE: In vitro and in vivo studies of methylseleninic acid: Evidence that a monomethylated selenium metabolite is critical for cancer chemoprevention. Cancer Res 60: 2882–2886, 2000
Dong Y, Ip C, Ganther H: Evidence of a field effect associated with mammary cancer chemoprevention by methylseleninic acid. Anticancer Res 22: 27–32, 2002
Jiang C, Wang Z, Ganther H, Lu J: Caspases as key executors of methyl selenium-induced apoptosis (anoikis) of DU-145 prostate cancer cells. Cancer Res 61: 3062–3070, 2001
Lu J, Jiang C, Kaeck M, Ganther H, Vadhanavikit S, Ip C, Thompson H: Dissociation of the genotoxic and growth inhibitory effects of selenium. Biochem Pharmacol 50: 213–219, 1995
Kaeck M, Lu J, Strange R, Ip C, Ganther HE, Thompson HJ: Differential induction of growth arrest inducible genes by selenium compounds. Biochem Pharmacol 53: 921–926, 1997
Wang Z, Jiang C, Ganther H, Lu J: Antimitogenic and proapoptotic activities of methylseleninic acid in vascular endothelial cells and associated effects on PI3K-AKT, ERK, JNK and p38 MAPK signaling. Cancer Res 61: 7171–7178, 2001
Dong Y, Ganther HE, Stewart C, Ip C: Identification of molecular targets associated with selenium-induced growth inhibition in human breast cells using cDNA microarrays. Cancer Res 62: 708–714, 2002
Gopalakrishna R, Gunimeda U, Chen Z-H: Cancer-preventive selenocompounds induce a specific redox modification of cysteine-rich regions in Ca2+-dependent isoenzymes of protein kinase C. Arch Biochem Biophys 348: 25–36, 1997
Gopalakrishna R, Chen Z-H, Gundimeda U: Selenocompounds induce a redox modulation of protein kinase C in the cell, compartmentally independent from cytosolic glutathione: Its role in inhibition of tumor promotion. Arch Biochem Biophys 348: 37–48, 1997
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Ip, C., Dong, Y. & Ganther, H.E. New Concepts in Selenium Chemoprevention. Cancer Metastasis Rev 21, 281–289 (2002). https://doi.org/10.1023/A:1021263027659
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DOI: https://doi.org/10.1023/A:1021263027659