Mechanisms of action of vitamin D in colon cancer. Issue 185 (January 2019)

• Record Type: Journal Article
• Authors: Ferrer-Mayorga, Gemma; Larriba, María Jesús; Crespo, Piero; Muñoz, Alberto
• Is Part Of: Journal of steroid biochemistry and molecular biology. Issue 185(2019)
• Page Start: 1
• Page End: 6
• Publication Date: 2019-01
• Subjects: Vitamin D -- Vitamin D receptor -- Calcitriol -- Colorectal cancer -- Wnt/β-catenin -- Cancer-associated fibroblasts -- Gut -- Microbiota; Steroid hormones -- Periodicals; Biochemistry -- Periodicals; Hormones -- Periodicals; Molecular Biology -- Periodicals; Hormones stéroïdes -- Périodiques; Steroid hormones; Periodicals; 572.579
• DOI: 10.1016/j.jsbmb.2018.07.002
• Languages: English
• ISSNs: 0960-0760

Abstract

Highlights: Colorectal cancer is the neoplasia that is most closely linked to vitamin D deficiency in epidemiological studies. Calcitriol inhibits the proliferation, migration, invasiveness and angiogenesis of colon carcinoma cells. Calcitriol promotes differentiation of colon carcinoma cells and sensitizes them to apoptosis. Calcitriol reduces the protumoral effects of colon cancer-associated fibroblasts. Calcitriol also regulates the biology of intestinal immune cells and affects the intestinal microbiota. Abstract: Colorectal cancer (CRC) is the neoplasia that is most frequently associated with vitamin D deficiency in epidemiological and observational studies in terms of incidence and mortality. Many mechanistic studies show that the active vitamin D metabolite (1α, 25-dihydroxyvitamin D3 or calcitriol) inhibits proliferation and promotes epithelial differentiation of human colon carcinoma cell lines that express vitamin D receptor (VDR) via the regulation of a high number of genes. A key action underlining this effect is the multilevel inhibition of the Wnt/β-catenin signaling pathway, whose abnormal activation in colon epithelial cells initiates and promotes CRC. Recently, our group has shown that calcitriol modulates gene expression and inhibits protumoral properties of patient-derived colon cancer-associated fibroblasts (CAFs). Accordingly, high VDR expression in tumor stromal fibroblasts is associated with longer survival of CRC patients. Moreover, many types of immune cells express VDR and are regulated by calcitriol, which probably contributes to its action against CRC. Given the role attributed to the intestinal microbiota in CRC and the finding that it is altered by vitamin D deficiency, an indirect antitumoral effect of calcitriol is also plausible at this level. In summary, calcitriol has an array of potential protective effects against CRC by acting on carcinoma cells, CAFs, immune cells and probably also the gut microbiota.