TY - JOUR
T1 - Methylseleninic acid, a potent growth inhibitor of synchronized mouse mammary epithelial tumor cells in vitro
AU - Sinha, Raghu
AU - Unni, Emmanual
AU - Ganther, Howard E.
AU - Medina, Daniel
PY - 2001/2/1
Y1 - 2001/2/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0035253830&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035253830&partnerID=8YFLogxK
U2 - 10.1016/S0006-2952(00)00545-1
DO - 10.1016/S0006-2952(00)00545-1
M3 - Article
C2 - 11172735
AN - SCOPUS:0035253830
SN - 0006-2952
VL - 61
SP - 311
EP - 317
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 3
ER -