Vitamin D3 insufficiency and colorectal cancer.

Traditionally the main recognized function of vitamin D has been calcium and phosphate homeostasis. Nevertheless, recent evidences have highlighted the importance of vitamin D3 as a protective agent against various cancers. The association between CRC and vitamin D3 was first suggested in ecologic studies, but further was confirmed by observational studies in humans and experimental studies in both animal models and cellular lines. The protective role of vitamin D3 against cancer has been attributed to its influence of on cell proliferation, differentiation, apoptosis, DNA repair mechanisms, inflammation and immune function. In its active (calcitriol) form (1,25-dihydroxyvitamin D3[1α,25-(OH)2D3]) vitamin D3 and the nuclear vitamin D receptor (VDR) regulate hundreds of genes including those coding for proteins involved in cell differentiation and cell proliferation. The current review addresses some of the key mechanisms that influence the biological actions of vitamin D and its metabolites. The insights derived from these mechanisms may aid in designing new uses for this hormone and its non-hypercalcemic derivatives in the treatment and/or prevention of CRC.