Mechanistic Effects of Calcitriol in Cancer Biology

Dı́az, Lorenza; Dı́az-Muñoz, Mauricio; García-Gaytán, Ana Cristina; Méndez, Isabel García

doi:10.3390/nu7065020

Cited by 105 publications

(101 citation statements)

References 202 publications

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“…Vitamin D actions as a steroid hormone are mediated through the vitamin D receptor (VDR) [57], which is a high affinity ligand-activated transcription factor [58]. Activated VDR heterodimerizes with the retinoid X receptor (RXR); this complex binds to the vitamin D response elements (VDREs) in the promoter of target genes and recruits coactivators and corepressors to induce or inhibit gene transcription [59].…”

Section: Vdr In Normal and In Malignant Colon Cellsmentioning

confidence: 99%

“…Activated VDR heterodimerizes with the retinoid X receptor (RXR); this complex binds to the vitamin D response elements (VDREs) in the promoter of target genes and recruits coactivators and corepressors to induce or inhibit gene transcription [59]. The expression and functionality of the VDR are mandatory for the anticancer effects of vitamin D; therefore, the loss of this transcription factor, as seen in some cells after malignant transformation, results in calcitriol resistance [58].…”

Section: Vdr In Normal and In Malignant Colon Cellsmentioning

confidence: 99%

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Vitamin D and Colorectal Carcinogenesis

Juniku-Shkololli¹

2017

A Critical Evaluation of Vitamin D - Clinical Overview

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Colorectal cancer is the second leading cause of cancer-related death in the Western industrialized world. Many epidemiological studies have shown a negative association between colorectal cancer incidence and vitamin D levels. It has been suggested that the antitumoral action of 1,25(OH) 2 D 3 in colorectal cancer relies on several mechanisms at the cellular level. This prompted us to evaluate expression of certain immunohistochemical markers during tumor progression in colorectal human tissue and to study for the first time the relationship between histological type and grade of colorectal tumors with the expression of these markers. The investigated markers were the ones responsible for apoptosis (PAK1 and p53), cell adhesion (beta-catenin), differentiation (p53), and proliferation (Ki67). We also analyzed the correlation of their expression with vitamin D blood levels in these patients. Our results showed that the expression of these biomarkers increased with progression from colorectal adenomas to carcinomas. Expression of PAK1, beta-catenin, and p53 in the nucleus correlated with advanced stages of carcinoma. Low vitamin D blood levels correlated with nuclear accumulation of p53, nuclear beta-catenin expression, and expression of Ki67.

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Section: Vdr In Normal and In Malignant Colon Cellsmentioning

confidence: 99%

Section: Vdr In Normal and In Malignant Colon Cellsmentioning

confidence: 99%

Vitamin D and Colorectal Carcinogenesis

Juniku-Shkololli¹

2017

A Critical Evaluation of Vitamin D - Clinical Overview

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“…The other reason is that vitamin D 3 is known to have anti-cancer and anti-inflammatory properties (Ness et al, 2015). Thus, vitamin D 3 regulates the cell cycle, induces apoptosis of cancer cells, promotes cell differentiation and works as a natural anti-inflammatory agent within the tumor microenvironment (Díaz et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Clinical Observation of a Novel, Complementary, Immunotherapeutic Approach based on Ketogenic Diet, Chondroitin Sulfate, Vitamin D<sub>3</sub>, Oleic Acid and a Fermented Milk and Colostrum Product

Schwalb

Taubmann

Hines³

et al. 2016

American Journal of Immunology

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Abstract:Here we describe the results of a novel type of complementary immunotherapy of cancer that is based on a combination of ketogenic diet, administration of an emulsion made of chondroitin sulfate, vitamin D 3 and oleic acid and of a fermented milk and colostrum product. The results here reported are consistent with current knowledge concerning the biological and clinical effects of each one of the elements used in the approach described in this study. Based on our results, we suggest that, among the different approaches to the complementary immunotherapy of cancer, those strategies based on ad-hoc formulated nutritional plans and on food supplements that stimulate the immune system and fight inflammation appear to be most promising. Thus, these approaches are characterized by inherent low toxicity and the possibility to use them in conjunction with conventional anti-cancer therapies targeting cancer cells such as radiation or chemotherapies.

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“…Thus, development of potential alternative or combinational colorectal cancer chemopreventive and therapeutic strategies is a paramount medical demand. To that end, vitamin D and its analogues are the most attractive agents in this setting (5,6).…”

Section: Introductionmentioning

confidence: 99%

“…There is a compelling body of evidence that calcitriol [1,25 (OH) 2 D 3 ], the active form of vitamin D, may not only reduce the risk of colorectal cancer and other human cancers but also repress the tumor cell resistance toward the cytotoxic effects of 5-FU and other anticancer chemotherapeutic agents, and regulate the activities of various genes that impact cancer cell proliferation, differentiation, apoptosis, angiogenesis, invasion, and drug resistance (5)(6)(7). However, such potential antitumor activity of calcitriol is achieved only when it is given in supraphysiologic doses that will lead to significant hypercalcemia and hypercalciuria side effects that hinder and impede its clinical usefulness for this purpose (7,8).…”

Section: Introductionmentioning

confidence: 99%

Paricalcitol Enhances the Chemopreventive Efficacy of 5-Fluorouracil on an Intermediate-Term Model of Azoxymethane-Induced Colorectal Tumors in Rats

El-Shemi

Refaat

Kensara

et al. 2016

Cancer Prevention Research

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Colorectal cancer is a common cancer with high mortality rate. Despite being the standard anti-colorectal cancer drug, 5-fluorouracil (5-FU) exhibits only limited therapeutic benefits. Herein, we investigated whether paricalcitol, a synthetic vitamin D analogue with potential antitumor properties, would enhance the chemopreventive efficacy of 5-FU on an intermediate-term (15 weeks) model of colorectal tumors induced by azoxymethane (AOM) in rats. After AOM injection, 5-FU was administered during the 9th and 10th weeks (12 mg/kg/day for 4 days, then 6 mg/kg every other day for another 4 doses), whereas paricalcitol (2.5 mg/kg/day; 3 days/week) was given from the 7th to the 15th week. At week 15, the animals were euthanized and their resected colons were examined macroscopically and microscopically. Quantitative RT-PCR was used to measure the transcription activities of Wnt, b-catenin, DKK-1, CDNK-1A, NF-kB, and COX-2 genes, and ELISA was used to quantify the protein levels of b-catenin, COX-2, HSP90, and VEGF. IHC was additionally used to measure b-catenin, HSP90, and inducible nitric oxide synthase (iNOS). Compared with their individual therapy, combination of 5-FU and paricalcitol showed more significant reducing effect on numbers of grown tumors and large aberrant crypts foci. Mechanistically, paricalcitol and 5-FU had cooperated together to repress the expression of procancerous Wnt, b-catenin, NF-kB, COX-2, iNOS, VEGF, and HSP-90 more, and to upregulate the expression of antitumorigenesis DKK-1 and CDNK-1A, compared with their monotherapies. Our findings suggest that combined use of paricalcitol with 5-FU exhibits an augmenting chemopreventive effect against colorectal tumors, and might potentially be useful for chemoprevention in colorectal cancer patients. Cancer Prev Res; 9(6); 491-501. Ó2016 AACR.

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Mechanistic Effects of Calcitriol in Cancer Biology

Cited by 105 publications

References 202 publications

Vitamin D and Colorectal Carcinogenesis

Vitamin D and Colorectal Carcinogenesis

Clinical Observation of a Novel, Complementary, Immunotherapeutic Approach based on Ketogenic Diet, Chondroitin Sulfate, Vitamin D<sub>3</sub>, Oleic Acid and a Fermented Milk and Colostrum Product

Paricalcitol Enhances the Chemopreventive Efficacy of 5-Fluorouracil on an Intermediate-Term Model of Azoxymethane-Induced Colorectal Tumors in Rats

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