Selenium and Cancer Stem Cells

Selenium (Se) is an essential micronutrient that functions as "redox gatekeeper"and homeostasis factor of normal and cancer cells. Epidemiology and experimental studies, in the last years suggested that both inorganic and organic forms of Se may have favorable health effects. In this regard, a protective action of Se on cellular systems that may help preventing cancer cell differentiation has been demonstrated, while the hypothesis that Se compounds may cure cancer and its metastatic diffusion appears speculative and is still a matter of investigation. Indeed, the overall actions of Se compounds in carcinogenesis are controversial. The recognition that cancer is a stem cell disease instigated major paradigm shifts in our basic understanding of cancer and attracted a great deal of interest. Although current treatment approaches in cancer are grounded in the need to kill the majority of cancer cells, targeting cancer stem cells (CSCs) may hold great potential in improving cancer treatment. In this respect, Se compounds have been demonstrated modulating numerous signaling pathways involved in CSC biology and these findings are now stimulating further research on optimal Se concentrations, most effective and cancer-specific Se compounds, and inherent pathways involved in redox and metabolic regulation of CSCs. In this review, we summarize the current knowledge about the effects of Se compounds on CSCs, by focusing on redox-dependent pathways and main gene regulation checkpoints that affect self-renewal, differentiation, and migration responses in this subpopulation of cancer cells.