Methylseleninic acid, a potent growth inhibitor of synchronized mouse mammary epithelial tumor cells in vitro.
Selenium compounds have been shown to be effective chemopreventive agents in several animal models and in cultured cells in vitro. It has been proposed that compounds able to generate monomethyl Se have an increased potential to inhibit cell growth. To test this hypothesis, methylseleninic acid (MSeA) and other compounds that could generate methylselenol rapidly were compared with Se compounds that do not generate monomethyl Se, using a well-characterized synchronized TM6 mouse mammary epithelial tumor model in vitro. MSeA at a low micromolar concentration inhibited TM6 growth after 10- to 15-min treatment times. Cells resumed growth after 24 hr but remained sensitive to the fresh addition of monomethyl Se-generators. Dimethyl selenide (DMSe), a putative metabolite of methylselenol, was inactive. Cells treated with 5 microM MSeA were arrested in G1. The effects of 5 microM MSeA on gene expression were evaluated using the Atlas mouse cDNA expression array. A 10-min exposure with MSeA caused a 2- to 3-fold change in the expression of three genes: laminin receptor 1 (decreased), integrin beta (decreased), and Egr-1 (increased). The results provide experimental support for the hypothesis that monomethylated forms of Se are the critical effector molecules in Se-mediated growth inhibition in vitro.
Sinha
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Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, 77030, Houston, TX, USA. rsinha@bcm.tmc.edu
Unni
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Ganther
H E
HE
Medina
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D
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004847:Epithelial Cells / Q000187:drug effects; D005260:Female; D015674:Mammary Neoplasms, Animal; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D016566:Organoselenium Compounds / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D016566:Organoselenium Compounds; D004247:DNA; C008493:methylselenic acid