In vitro growth inhibition of mouse mammary epithelial tumor cells by methylseleninic acid: Involvement of protein kinases
- 6 November 2008
- journal article
- research article
- Published by Wiley in Molecular Nutrition & Food Research
- Vol. 52 (11), 1281-1288
- https://doi.org/10.1002/mnfr.200700356
Abstract
Methylseleninic acid (MSeA) is a synthetic organoselenium form known to be effective against mammary carcinogenesis in vivo. Using the synchronized mouse mammary epithelial tumor cell (TM6) model, we have previously shown that 5 μM MSeA significantly inhibits cell growth and induces a reversible growth arrest in the G1 phase. In the present study, we examined the effects of MSeA on Rb, cyclin dependent kinase 2 (cdk2), cdk4, cyclin E and cyclin D1. Growth arrest of cells was accompanied by a reduction in total cdk2 kinase and cyclin E‐associated cdk2 kinase activities. The p27 levels associated with cdk2 were elevated during the cell cycle. In addition, growth inhibition correlated with a relative increase in the hypophosphorylated form of Rb in MSeA‐treated cells and Egr1 was elevated in MSeA‐treated cells. The KinetworksTM Protein Kinase Screen (KPKS 1.0) was used to examine 75 protein kinases. MSeA treatment resulted in differential expression of several protein–serine/threonine kinases, protein–tyrosine kinases and protein–threonine/tyrosine kinases. Some of these kinases are being reported for the first time as being altered by MSeA. The outcome of these experiments will be of significance since these kinases are known to be involved in survival and/or apoptotic pathways of tumor cells.Keywords
This publication has 19 references indexed in Scilit:
- Monomethylated selenium inhibits growth of LNCaP human prostate cancer xenograft accompanied by a decrease in the expression of androgen receptor and prostate-specific antigen (PSA)The Prostate, 2006
- Comparison of the Chemopreventive Efficacies of 1,4-phenylenebis(methylene)selenocyanate and Selenium-Enriched Yeast on 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone Induced Lung Tumorigenesis in A/J MouseNutrition and Cancer, 2003
- Bioactivation of Chemopreventive Selenocysteine Se-Conjugates and Related Amino Acids by Amino Acid Oxidases Novel Route of Metabolism of Selenoamino AcidsChemical Research in Toxicology, 2001
- Methylseleninic acid, a potent growth inhibitor of synchronized mouse mammary epithelial tumor cells in vitroBiochemical Pharmacology, 2001
- Effects of Selenium Supplementation for Cancer Prevention in Patients With Carcinoma of the SkinJAMA, 1996
- Cancer Cell CyclesScience, 1996
- Cell Cycle Control of DNA ReplicationScience, 1996
- How Proteolysis Drives the Cell CycleScience, 1996
- Cellular and metabolic effects of triphenylselenonium chloride in a mammary cell culture modelCarcinogenesis: Integrative Cancer Research, 1995
- Comparison of selenium and sulfur analogs in cancer preventionCarcinogenesis: Integrative Cancer Research, 1992