Methylseleninic acid, a potent growth inhibitor of synchronized mouse mammary epithelial tumor cells in vitro

Raghu Sinha, Emmanual Unni, Howard E. Ganther, Daniel Medina

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

Abstract

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 μM MSeA were arrested in G1. The effects of 5 μM 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.

Original languageEnglish (US)
Pages (from-to)311-317
Number of pages7
JournalBiochemical Pharmacology
Volume61
Issue number3
DOIs
StatePublished - Feb 1 2001

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Pharmacology

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