Supranutritional Selenomethionine but not Selenite Reduces Malignant Cell Transformation

The trace element selenium is essential to human health and has long been discussed to modulate the carcinogenic process. So far, the functions of selenium and selenoproteins have been mainly studied in already transformed cancer cells. The aim of this study was, therefore, to characterize the role of selenium during the neoplastic transformation process in a concentration- and species-specific manner using the BALB/c cell transformation assay. This assay mimics the initiation and promotion phase of BALB/c cells (murine fibroblasts) treated with a tumor initiator (MCA) and promoter (TPA) leading to malignant cell foci development. In parallel, cells were supplied with selenite or selenomethionine using suboptimal, adequate or supranutritional concentrations (0.01-1 μM). The supranutritional selenomethionine concentration reduced malignantly transformed foci, accompanied by higher NQO1 levels suggesting an upregulation of antioxidant NRF2 target genes. In contrast, treatment with the same concentration of selenite appeared to increase malignant transformation which was associated with higher intracellular selenium concentrations. Neither suboptimal nor adequate concentrations of either selenium species affected malignant cell transformation even though selenoprotein expression was modulated. Overall, the current data suggest that high concentrations of selenium have different effects on malignant cell transformation depending on the distinct selenium species applied.