Se-methylselenocysteine inhibits phosphatidylinositol 3-kinase activity of mouse mammary epithelial tumor cells in vitro

Emmanual Unni,Wai-Kwan Alfred Yung,Dimpy Koul,Raghu Sinha

doi:10.1186/bcr1276

Abstract

IntroductionSe-methylselenocysteine (MSC), a naturally occurring selenium compound, is a promising chemopreventive agent against in vivo and in vitro models of carcinogen-induced mouse and rat mammary tumorigenesis. We have demonstrated previously that MSC induces apoptosis after a cell growth arrest in S phase in a mouse mammary epithelial tumor cell model (TM6 cells) in vitro. The present study was designed to examine the involvement of the phosphatidylinositol 3-kinase (PI3-K) pathway in TM6 tumor model in vitro after treatment with MSC.MethodsSynchronized TM6 cells treated with MSC and collected at different time points were examined for PI3-K activity and Akt phosphorylation along with phosphorylations of Raf, MAP kinase/ERK kinase (MEK), extracellular signal-related kinase (ERK) and p38 mitogen-activated protein kinase (MAPK). The growth inhibition was determined with a [3H]thymidine incorporation assay. Immunoblotting and a kinase assay were used to examine the molecules of the survival pathway.ResultsPI3-K activity was inhibited by MSC followed by dephosphorylation of Akt. The phosphorylation of p38 MAPK was also downregulated after these cells were treated with MSC. In parallel experiments MSC inhibited the Raf–MEK–ERK signaling pathway.ConclusionThese studies suggest that MSC blocks multiple signaling pathways in mouse mammary tumor cells. MSC inhibits cell growth by inhibiting the activity of PI3-K and its downstream effector molecules in mouse mammary tumor cells in vitro.

Highlights

Se-methylselenocysteine (MSC), a naturally occurring selenium compound, is a promising chemopreventive agent against in vivo and in vitro models of carcinogen-induced mouse and rat mammary tumorigenesis
In parallel experiments MSC inhibited the Raf–MAP kinase/extracellular signal-related kinase (ERK) kinase (MEK)–ERK signaling pathway. These studies suggest that MSC blocks multiple signaling pathways in mouse mammary tumor cells
For the present investigation we examined the effects of MSC on the components of the phosphatidylinositol 3-kinase (PI3-K)–Akt and Raf–MEK–ERK pathways to improve our understanding of the mechanisms of growth inhibition in the synchronized TM6 mouse mammary tumor cell line

Summary

Introduction

Se-methylselenocysteine (MSC), a naturally occurring selenium compound, is a promising chemopreventive agent against in vivo and in vitro models of carcinogen-induced mouse and rat mammary tumorigenesis. We have demonstrated previously that MSC induces apoptosis after a cell growth arrest in S phase in a mouse mammary epithelial tumor cell model (TM6 cells) in vitro. Several organic and inorganic selenium compounds have been reported to be effective chemopreventive agents against multiple models of mammary tumorigenesis in both the mouse and the rat [1,2,3,4,5]. Se-methylselenocysteine (MSC) is a less toxic organic selenium compound occurring naturally. It is the major form of selenium compound in selenium-enriched garlic, onions and broccoli [17]. MSC inhibits cell growth in several mouse mammary tumor cell lines [19,20] and human

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Conclusion