© 2004 by Oxford University Press
© 2004 Oxford University Press
CORRESPONDENCE |
Re: Science Peels the Onion of Selenium Effects on Prostate Carcinogenesis
Correspondence to: Boguslaw Lipinski, PhD, Joslin Diabetes Center, Harvard Medical School, One Joslin Place, Boston, MA 02215 (e-mail: boguslaw_lipinski{at}joslin.harvard.edu)
In a recent issue of the Journal, Taylor et al. (1) argued that selenium appears to play an important role not only in preventing various cancers but also in some degenerative diseases. Most of the data on the cancer prevention and cancer reduction effects of selenium are derived from epidemiologic studies (2). However, despite strong evidence for the importance of selenium in carcinogenesis, very little is known about its mechanism of action. Taylor et al. (1) suggested that selenium effects can be indirect via incorporation into selenoproteins or direct via selenium metabolites. These two pathways may or may not explain why some forms of selenium are more active than others in inhibiting cancer cell growth.
Two forms of selenium—organic and inorganic—are used predominately as cancer chemopreventive agents. Among the organic forms, selenomethionine is the most frequently used in in vitro and in vivo anticancer studies. However, among the two commonly used inorganic forms only sodium selenite (Se4+) has anticancer properties (3). The other inorganic form, selenate (Se6+), has practically no activity (3). This difference in activity may be explained in terms of the different chemical reactivities of these two compounds. Although they differ by only one atom of oxygen in their structure, only selenite is an oxidant—an obvious paradox because selenium compounds and selenoproteins are generally considered antioxidants. However, the oxidant properties of selenite are manifested only under specific redox conditions, namely, selenite oxidizes polythiol but not monothiol compounds to corresponding disulfides (4). This specific oxidative property of selenite may also explain the inhibitory effect of sodium selenite on the crosslinking of plasma proteins induced by transplantable mouse tumor tissue (5). Compared with the surfaces of normal cells, the surfaces of tumor cells, such as Ehrlich ascites tumor cells, are enriched with sulfhydryl groups (6). Thus, it is possible that the specific ability of selenite to oxidize sulfhydryl groups of cell surface proteins, thereby potentially blocking protein polymerization, may be responsible for the anticancer properties of selenite. However, despite considerable data on the use of selenium compounds in cancer prevention and treatment, few investigations have compared organic and inorganic forms of selenium. To my knowledge, only one in vitro study with prostate cancer cell lines has shown sodium selenite, at any given concentration, to be a more potent inhibitor of growth than selenomethionine (7).
In conclusion, it appears that a specific form of inorganic selenium, sodium selenite, has unique biologic properties that may warrant its use as an anticancer agent. However, sodium selenite needs first to be thoroughly evaluated in vitro and in vivo in different types of cancer.
NOTES
Drs. Lippman and Taylor declined to respond to the correspondence.
REFERENCES
1 Taylor PR, Parnes HL, Lippman SM. Science peels the onion of selenium effects on prostate carcinogenesis. J Natl Cancer Inst 2004;9:645–7.
2 Whanger PD. Selenium and its relationship to cancer: an update. Br J Nutr 2004;91:11–28.[CrossRef][Web of Science][Medline]
3 Batist G, Katki AG, Klecker RW Jr, Myers CE. Selenium-induced cytotoxicity of human leukemia cells: interaction with reduced glutathione. Cancer Res 1986:46:5482–5.
4 Gopalakrishna R, Gundimeda U, Chen ZH. Cancer-preventive selenocompounds induce a specific redox modification of cysteine-rich regions in Ca(2+)-dependent isoenzymes of protein kinase C. Arch Biochem Biophys 1997;348:25–36.[CrossRef][Web of Science][Medline]
5 Lipinski B, Egyud LG. Thiol-induced crosslinking of human blood proteins. Implications for tumor immunity. Bioorg Med Chem Lett 1992;2:919–24.[CrossRef]
6 Mehrishi JN, Grassetti DR. Sulphydryl groups on the surface of intact Ehrlich ascites tumour cells, human blood platelets and lymphocytes. Nature 1969;224:563–4.[Medline]
7 Menter DG, Sabichi AL, Lippman SM. Selenium effects on prostate cell growth. Cancer Epidemiol Biomarkers Prev 2000;9:1171–82.
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J Natl Cancer Inst 2004 96: 645-647.
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