Abstract 4881: Influence of polyphenols on selenoprotein expression in human colon cancer cells.

Abstract

Selenium, an essential micronutrient, is recognized as a cancer protective agent that functions through low-molecular weight selenocompounds, and, importantly, through selenoproteins. Previous studies suggest that the 15 kDa selenoprotein (Sep15), a gene polymorphic in humans, has an important role in colon cancer in vivo, and that reduction of Sep15 in human HCT116 colon cancer cells reverses their cancer phenotype. Our diet contains a wide array of nutrients, and it is conceivable that these share molecular targets with selenium and regulate selenoprotein expression. The selenoproteins Thioredoxin Reductase 1 (TR1) and Glutathione Peroxidase (GPx) 2 are regulated by the transcription factor Nrf2, whereas GPx1 is not. Some dietary compounds, e.g., Sulforaphane, are known Nrf2-inducers, impacting expression of TR1 and GPx2. However, the effect of Sulforaphane and many polyphenols on other selenoproteins, or, how other polyphenols influence TR1 and GPx2 remains to be elucidated. Using HCT116 cells, we are investigating the effects of polyphenols and Sulforaphane on selenoprotein expression. Cells with wild type or down-regulated expression of Sep15 were exposed to 5 μM Sulforaphane or 20 μM 5,7-Dimethoxyflavone (5,7-DMF) for 48 hours. Subsequently, mRNA was isolated and examined with real-time RT-PCR. Our preliminary results suggest that, Sulforaphane exposure resulted in a slight increase of TR1 mRNA in both control and shSep15 cells, but not GPx2. Interestingly, 5,7-DMF exposure resulted in increased GPx1 (P<0.01) and GPx2 (P>0.05) mRNA in control cells. Surprisingly, GPx2 mRNA appeared significantly down-regulated (P<0.01) in shSep15 cells compared to DMSO treated cells, whereas GPx1 mRNA appeared unaffected. Western blotting and activity measurements are currently underway to support these results. Citation Format: Sarah E. Galinn, Lindsay C. Rosenthal, Steven M. Barsotti, Petra A. Tsuji. Influence of polyphenols on selenoprotein expression in human colon cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4881. doi:10.1158/1538-7445.AM2013-4881