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 i n several animal models and in cultured cells in vitro. It has been propose d that compounds able to generate monomethyl Se have an increased potential to inhibit cell growth. To test this hypothesis, methylseleninic acid (MSe A) and other compounds that could generate methylselenol rapidly were compa red with Se compounds that do not generate monomethyl Se, using a well-char acterized synchronized TM6 mouse mammary epithelial tumor model in vitro. M SeA at a low micromolar concentration inhibited TM6 growth after 10- to 15- min treatment times. Cells resumed growth after 24 hr but remained sensitiv e to the fresh addition of monomethyl Se-generators. Dimethyl selenide (DMS e), a putative metabolite of methylselenol. was inactive. Cells treated wit h 5 muM MSeA were arrested in G(1). The effects of 5 muM MSeA on gene expre ssion 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 t hat monomethylated forms of Se are the critical effector molecules in Se-me diated growth inhibition in vitro. (C) 2001 Elsevier Science Inc. All right s reserved.