Vitamin D Compounds and Cancer Stem Cells in Cancer Prevention

Cancer is a disease process comprising distinct stages, from initiation to promotion and progression to metastasis, where multiple factors can enhance or delay each stage during the development. Cancer stem cells, a small subpopulation of cancer cells with self-renewal and differentiating capacity, have been suggested to be involved in initiation, progression, and recurrence of tumors. Thus, targeting cancer stem cells may be important for cancer prevention. Natural products, hormones, nutritional and dietary factors have the ability to change the fate of cancer stem cells. Revealing the effect of compounds on the regulation of self-renewal or differentiation of cancer stem cells in malignancies, including breast, colorectal, prostate, and pancreatic cancers, could be useful for implementing novel cancer preventive approaches. Vitamin D compounds are known to induce hematopoietic stem cells to become more functionally differentiated cells, and differentiation therapy has been well established in blood cancers. Based on the differentiating and anti-proliferating effects, targeting cancer stem cells by vitamin D compounds may potentially contribute to the inhibition of solid tumors. In this chapter, we review the role of vitamin D compounds in regulation of cancer stem cell markers such as CD44, ALDH1, CD24, CD133, EpCAM, CD49f, as well as cancer stem cell signaling pathways including Notch, Wnt or Hedgehog in cancer. Further, diverse structures of vitamin D compounds as well as combination strategies are considered for improving differentiating activities and cancer preventive effects. Understanding the role of vitamin D compounds targeting cancer stem cells may support their potential use as cancer preventive and therapeutic agents.