Submitted to: Biofactors
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 26, 2008
Publication Date: November 7, 2008
Repository URL: http://handle.nal.usda.gov/10113/46631
Citation: Zeng, H., Botnen, J.H. 2008. Selenium is critical for cancer-signaling gene expression but not cell proliferation in human colon Caco-2 cells. Biofactors. 31(2007):155-164 Interpretive Summary: Selenium (Se) is an essential dietary component for mammals including humans, and there is increasing evidence for the efficacy of certain forms of selenium as cancer-chemopreventive compounds. The essential role of Se in growth of most mammalian cells is well recognized but certain cancer cells appear to have acquired a survival advantage under Se-deficient conditions, and little is known about the role of Se in these cancer cells. To understand molecular basis of Se-anticancer effect at cellular nutritional dose (nmol/L), we generated Se-deficient Caco-2 cells with a serum gradual reduction method in the present study. Interestingly, there were not detectable differences on cell growth, cell cycle progression between Se-deficient cells and cells supplemented with 500 nmol/L Se in media. Our data suggest, for the first time, that Caco-2 colon cancer cells have acquired a survival advantage when cultured in Se-deficient media. Further study demonstrated that Se increased the expression of tumor suppressor-related genes (IGFBP3, HHIP) and decreased pro-inflammatory gene (CXC L9, HSPB2) expression at cellular nutritional Se dose. Although Caco-2 colon cells were resistant to Se deprivation, our findings indicate that cellular nutritional dose (nmol/L) of Se still plays a critical role in its anticancer effect. The information will be useful information for scientists and health-care professionals who are interested in Se and cancer prevention.
Technical Abstract: Selenium (Se) is an anticancer nutrient, and the essential role of Se in growth of most mammalian cells is well recognized but certain cancer cells appear to have acquired a survival advantage under conditions of Se-deficiency. The objective of the present study is to understand the molecular basis of Se-anticancer effects at a cellular nutritional dose (nmol/L). We generated Se-deficient colon Caco-2 cells by gradually reducing serum in the media because serum contains a trace amount of Se, which is sufficient to maintain the expression of cellular selenoproteins such as glutathione peroxidase (GPx). The GPx activity of Se-deficient Caco-2 cells was 10.8 mU/mg protein compared to 133.6~146.3 mU/mg protein in Caco-2 cells supplemented with 500 nmol/L selenite, se-(methyl)selenocysteine or selenomethionine (three tested Se chemical forms) after 7- day culture in serum free media. Interestingly, there were no detectable differences on cell growth, cell cycle progression between Se-deficient cells and cells supplemented with 500 nmol/L Se. This observation demonstrates, for the first time, that colon Caco-2 cancer cells have acquired a survival advantage under Se-deficient culture condition. To examine differential cancer signaling-gene expression between Se-deficient and Se-supplemented cells, we employed a cancer signal pathway-specific array assay coupled with the real time PCR analysis. Our data suggest that Se up-regulates the expression of humoral defense gene (A2M) and tumor suppressor-related genes (IGFBP3, HHIP) and but down-regulates pro-inflammatory gene (CXC L9, HSPB2) expression at cellular nutritional Se doses, even though colon Caco-2 cells were resistant to Se deprivation, and the change of IGFBP3 mRNA level occurs in human colon tumor tissues.