Mechanisms of action of vitamin D in colon cancer

Ferrer-Mayorga, Gemma; Larriba, María Jesús; Crespo, Piero; Múñoz, Alberto

doi:10.1016/j.jsbmb.2018.07.002

Cited by 112 publications

(96 citation statements)

References 103 publications

(95 reference statements)

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“…75 LCA is one of toxic secondary bile acids to cells, rarely reabsorbed and mainly passes into the colon. 150 Activation of the Wnt/β-catenin pathway is the common early event in the majority of CRC. 78 VDR is activated by LCA and is involved in detoxification of the toxic bile acid.…”

Section: Bile Acids-activated Receptorsmentioning

confidence: 99%

“…But it decreased at advanced tumor stages and lost in metastatic cancers. 150 Activation of the Wnt/β-catenin pathway is the common early event in the majority of CRC. 151 Compared to Apc Min/+ mice, tumors in Apc min/+ VDR −/− had a larger size and increased expression of β-catenin, cyclin D1, phosphorylated Stat-3 and MSH-2, and decreased Stat-1.…”

Section: Bile Acids-activated Receptorsmentioning

confidence: 99%

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The gut microbiota at the intersection of bile acids and intestinal carcinogenesis: An old story, yet mesmerizing

Song

Khan

et al. 2019

Intl Journal of Cancer

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The prevalence of colorectal cancer (CRC) has markedly increased worldwide in the last decade. Alterations of bile acid metabolism and gut microbiota have been reported to play vital roles in intestinal carcinogenesis. About trillions of bacteria have inhabited in the human gut and maintained the balance of host metabolism. Bile acids are one of numerous metabolites that are synthesized in the liver and further metabolized by the gut microbiota, and are essential in maintaining the normal gut microbiota and lipid digestion. Multiple receptors such as FXR, GPBAR1, PXR, CAR and VDR act as sensors of bile acids have been reported. In this review, we mainly discussed interplay between bile acid metabolism and gut microbiota in intestinal carcinogenesis. We then summarized the critical role of bile acids receptors involving in CRC, and also addressed the rationale of multiple interventions for CRC management by regulating bile acids–microbiota axis such as probiotics, metformin, ursodeoxycholic acid and fecal microbiota transplantation. Thus, by targeting the bile acids–microbiota axis may provide novel therapeutic modalities in CRC prevention and treatment.

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Section: Bile Acids-activated Receptorsmentioning

confidence: 99%

Section: Bile Acids-activated Receptorsmentioning

confidence: 99%

The gut microbiota at the intersection of bile acids and intestinal carcinogenesis: An old story, yet mesmerizing

Song

Khan

et al. 2019

Intl Journal of Cancer

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“…Epidemiological and preclinical studies suggest an association between vitamin D deficiency and inflammatory bowel diseases (IBD), various extraskeletal disorders, and several neoplasias, particularly colorectal cancer (CRC) [1,3,4]. Supporting this, experimental results in immortal carcinoma cell lines and animal models of CRC demonstrate a multilevel protective action of calcitriol and other VDR agonists [3,5].…”

Section: Introductionmentioning

confidence: 97%

Vitamin D differentially regulates colon stem cells in patient‐derived normal and tumor organoids

et al. 2019

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Intestine is a major target of vitamin D and several studies indicate an association between vitamin D deficiency and inflammatory bowel diseases (IBD), but also increased colorectal cancer (CRC) risk and mortality. However, the putative effects of 1α,25‐dihydroxyvitamin D3 (calcitriol), the active vitamin D metabolite, on human colonic stem cells are unknown. Here we show by immunohistochemistry and RNAscope in situ hybridization that vitamin D receptor (VDR) is unexpectedly expressed in LGR5+ colon stem cells in human tissue and in normal and tumor organoid cultures generated from patient biopsies. Interestingly, normal and tumor organoids respond differentially to calcitriol with profound and contrasting changes in their transcriptomic profiles. In normal organoids, calcitriol upregulates stemness‐related genes, such as LGR5, SMOC2, LRIG1, MSI1, PTK7, and MEX3A, and inhibits cell proliferation. In contrast, in tumor organoids calcitriol has little effect on stemness‐related genes while it induces a differentiated phenotype, and variably reduces cell proliferation. Concordantly, electron microscopy showed that calcitriol does not affect the blastic undifferentiated cell phenotype in normal organoids but it induces a series of differentiated features in tumor organoids. Our results constitute the first demonstration of a regulatory role of vitamin D on human colon stem cells, indicating a homeostatic effect on colon epithelium with relevant implications in IBD and CRC.

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“…In addition, several observational studies have reported associations between low vitamin D levels and the incidence of, and mortality due to, CRC [48]. Mechanistic studies show that, through gene regulation, 1α,25-dihydroxyvitamin D3 or calcitriol (active vitamin D metabolite) inhibits the proliferation and promotes the epithelial differentiation of human colon carcinoma cell lines that express vitamin D receptors [49]. Therefore, improving vitamin D status could potentially contribute to reducing the risk of CRC.…”

Section: Discussionmentioning

confidence: 99%

Hospital-Based Preliminary Observations of Dietary Intake and Physical Activity in Saudi Patients with Colorectal Polyps: A Call for Nutrition Care Integration after Polypectomy Procedure

Alkhaldy

2020

Gastrointestinal Disorders

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Aim: In Saudi Arabia, the incidence of colorectal cancer (CRC) is increasing. Lifestyle modification, including diet and physical activity, is as important as the standard procedure of colonoscopy screening in reducing CRC development. I explored the dietary intake, physical activity, and selected nutritional biomarkers in Saudi patients with colorectal polyps, a precursor of CRC. Methods: Thirty polypectomy patients (aged 35–84 years) were recruited from an endoscopy unit at King Abdulaziz University Hospital. Demographic, anthropometric, physical activity, and food frequency data were collected. Plasma C-reactive protein, serum 25-hydroxy vitamin D, and folate levels were measured. Results: The median body mass index (BMI) of the patients was within the overweight cut-off range. The median consumption of carbohydrate and protein was within the recommended dietary allowance (RDA). Median fat consumption was above the RDA, while median fiber intake was below the RDA. Patients met the recommended servings/day of fruits, vegetables, dairy products, and protein but exceeded the recommended intake of fats and sweets. Most patients were non-active, with an inadequate level of serum vitamin D. Conclusion: We observed several risk factors previously associated with CRC, including low levels of physical activity, serum vitamin D, and fiber intake, and high BMI and fat intake among polypectomy patients.

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Mechanisms of action of vitamin D in colon cancer

Cited by 112 publications

References 103 publications

The gut microbiota at the intersection of bile acids and intestinal carcinogenesis: An old story, yet mesmerizing

The gut microbiota at the intersection of bile acids and intestinal carcinogenesis: An old story, yet mesmerizing

Vitamin D differentially regulates colon stem cells in patient‐derived normal and tumor organoids

Hospital-Based Preliminary Observations of Dietary Intake and Physical Activity in Saudi Patients with Colorectal Polyps: A Call for Nutrition Care Integration after Polypectomy Procedure

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