Selenium Is Critical For The Regulation Of Tumor Suppressor And Pro-Inflammatory Gene Expression In Human Colon Caco-2 Cells

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. 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 not detectable differences on cell growth, cell cycle progression between Se‐deficient and Se‐supplemented cells. However, cancer signal pathway‐specific array assay and the real time PCR analysis demonstrated that Se increased the expression of humoral defense gene (A2M) and tumor suppressor‐related genes (IGFBP3, HHIP) but decreased pro‐inflammatory gene (CXC L9, HSPB2) expression at cellular nutritional Se doses, even though colon Caco‐2 cells were resistant to Se deprivation.