Using components of the vitamin D pathway to prevent and treat colon cancer.

The objective of this review was to analyze the components of vitamin D and their potential usefulness in preventing and treating colorectal cancer. The active form of vitamin D, 1α,25(OH(2) )D(3) , targets the wnt/β-catenin pathway by upregulating key tumor suppressor genes such as E-cadherin, which promotes an epithelial phenotype, but this is only possible when the vitamin D receptor (VDR) is present. Colorectal cell lines have shown that VDR expression levels decrease in the later stages of colon cancer. In colorectal cancers with low VDR expression, treatments to increase VDR expression could target alterations at the genomic and epigenomic levels by modulating transcription factors such as SNAIL1 and by utilizing histone deacetyltransferase inhibitors, respectively. Finally, epidemiological studies suggest that the current US Recommended Dietary Allowance should be increased to 2,000 IU in order to raise serum 25(OH)D(3) levels above 30 ng/mL. This increase in vitamin D status can be obtained most efficiently from sun exposure or vitamin D supplementation. In summary, vitamin D and its metabolites could be utilized in strategies to treat and prevent colon cancer.