Organic and inorganic selenium compounds inhibit mouse mammary cell growth in vitro by different cellular pathways.
Selenium, both organic and inorganic forms, inhibit mammary tumorigenesis in vivo and mammary cell growth in vitro. In the present study, sodium selenite was compared to methylselenocysteine (MSC) for their individual effects on cell growth, cdc2/cdk2 kinase activities and the levels of cyclins D1, E and A bound to cdk2 in a mouse mammary epithelial cell culture model. Selenite arrested the growth of cells in S-G2-M phase in contrast to MSC which arrested or delayed the cells in G1. In MSC-treated cells there was a 57% drop in the cdk2 kinase activity accompanied by a 73.5% decrease in cyclin E-cdk2 content as compared to the control cells. Selenite treatment increased the cdk2 kinase activity by 30% without any appreciable change in either of the cyclins D1, E or A bound to cdk2 when compared to the control cells. These data support the hypothesis that selenite and MSC have distinct modes of action in the inhibition of cell growth in vitro. Selenite has a strong genotoxic effect on the tumor cells; in contrast, MSC appears to inhibit cell growth via specific inhibition of cell cycle regulatory proteins.
Sinha
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Department of Cell Biology, Baylor College of Medicine, TX 77030, USA.
Said
T K
TK
Medina
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D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D042846:CDC2-CDC28 Kinases; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017279:Selenocysteine / Q000627:therapeutic use*; D018038:Sodium Selenite / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D017279:Selenocysteine; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495893:Cdk2 protein, mouse; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; D018038:Sodium Selenite