Vitamin D and Colon Cancer

Abstract

The most active vitamin D metabolite, 1 ,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3), is a pleiotropic hormone with wide regulatory actions. Classically, vitamin D deficiency was known to alter calcium and phosphate metabolism and bone biology. In addition, recent epidemiological and experimental studies support the association of vitamin D deficiency with a large variety of human diseases, and particularly with the high risk of colorectal cancer. By regulating the expression of many genes via several mechanisms, 1,25(OH) 2 D 3 induces differentiation, controls the detoxification metabolism and cell phenotype, sensitizes cells to apoptosis, and inhibits the proliferation of cultured human colon carcinoma cells. Consistently, 1,25(OH) 2 D 3 and several of its analogues decrease intestinal tumourigenesis in animal models. Molecular, genetic, and clinical data in humans are scarce but they suggest that vitamin D is protective against colon cancer. Clearly, the available evidence warrants new, well-designed, large-scale trials to clarify the role of vitamin D in the prevention and/or therapy of this important neoplasia.

Comparative Study of Organoids from Patient-Derived Normal and Tumor Colon and Rectal Tissue

“…The top calcitriol-upregulated genes in both types of organoids were the known calcitriol targets CYP24A1 , CYP3A4 , TRPV6, and PRSS33 . Among the top-downregulated genes, we found P2RX1 and DKK4, with the latter described as repressed by calcitriol in colon carcinoma cells [ 55 , 56 ]. DUOXA2 , CEACAM7 , and the proto-oncogene ADRA1B [ 57 ] were downregulated by calcitriol in rectal tumor organoids, but upregulated in colon tumor organoids.…”

Mechanisms of action of vitamin D in colon cancer

“…Interestingly, some studies have linked polymorphisms of genes of the vitamin D system (VDR, CYP27B1, CYP24A1, GC, DHCR7 and CYP2R1) to CRC prognosis or response to therapy [10][11][12][13]. Various studies using animals, including some that analyze the effect of diets with high or low vitamin D (and calcium) and carcinogen content, and others with genetically-modified or xenotransplanted mice, support a beneficial effect of vitamin D, calcitriol or its analogues on colorectal tumorigenesis (reviewed in [14]). Altogether, these findings suggest a protective action of vitamin D against CRC by either reducing risk and/or attenuating the tumorigenic process.…”

“…Concordantly, VDR agonists potentiate the effect of chemotherapeutic agents in cultured cells and animal models of CRC (reviewed in [14]).…”

Alternative binding sites at the vitamin D receptor and their ligands

“…The biochemical changes induced by VDR ligands in cancer cells include gene regulation, activation and inhibition of enzymatic pathways, and overall changes in cell differentiation and proliferation (Van Driel et al, 2018). The specific changes for different cancers were recently reviewed for leukemia (Studzinski et al, 2018), breast cancer (Beaudin and Welsh, 2018), prostate, renal, and bladder cancer (Trump, 2018), colon cancer (Barbchano et al, 2018), skin cancer (Ransohoff et al, 2018), and lung cancer (Shaurova et al, 2018). In addition, some vitamin D analogs have anti-inflammatory properties that have prompted detailed investigations on the role VDR and its ligands play in inflammation and immunity summarized by (Mann et al, 2018).…”