Current progress in using vitamin D and its analogs for cancer prevention and treatment

Cheung, Florence Shin Gee; Lovicu, Frank J.; Reichardt, Juergen K.V.

doi:10.1586/era.12.53

Cited by 38 publications

(27 citation statements)

References 128 publications

(142 reference statements)

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“…Some observational, preclinical, and clinical studies strongly suggest a beneficial role for vitamin D, but other studies do not support this hypothesis (32). Although the studies are inconsistent, accumulating evidence strongly suggest that vitamin D exhibit multiple anticancer actions and provide justification for the study of vitamin D 3 in cancer prevention and treatment (33).…”

Section: Discussionmentioning

confidence: 99%

1α,25-Dihydroxyvitamin D3 Inhibits Esophageal Squamous Cell Carcinoma Progression by Reducing IL6 Signaling

Chen

Hsieh

et al. 2015

Molecular Cancer Therapeutics

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The aim of this study was to highlight the role of 1a,25-dihydroxyvitamin D3 (calcitriol) in esophageal squamous cell carcinoma (SCC). The human esophageal SCC cell lines CE81T and TE2 were selected for cellular and animal experiments to investigate the changes in tumor behavior after calcitriol supplementation and the underlying mechanisms. Moreover, we evaluated the relationship between calcitriol supplementation, myeloid-derived suppressor cell (MDSC) recruitment, IL6 levels, and tumor progression by a 4-nitroquinoline 1-oxide (4-NQO)-induced esophageal tumor animal model. In this study, we demonstrated that calcitriol supplementation inhibited aggressive tumor behavior both in vitro and in vivo. The underlying changes included increased cell death, a lower degree of epithelial-mesenchymal transition, and inhibited IL6 signaling. In the 4-NQOinduced esophageal tumor animal model, increased IL6 and MDSC recruitment were linked with invasive esophageal tumors. Supplementation with calcitriol attenuated the level of IL6, the induction of MDSCs, and the incidence of 4-NQO-induced invasive tumors. Moreover, the IL6-induced changes in C57 mice, including augmented MDSC recruitment, increased levels of ROS and p-Stat3 in MDSCs, and higher suppressive function of MDSCs in T-cell proliferation, which were abrogated by calcitriol supplementation. On the basis of our results, we concluded that calcitriol abrogated the IL6-induced aggressive tumor behavior and MDSC recruitment to inhibit esophageal tumor promotion. Therefore, we suggest that supplementation with vitamin D 3 may be a promising strategy for the prevention and treatment of esophageal SCC.

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Section: Discussionmentioning

confidence: 99%

1α,25-Dihydroxyvitamin D3 Inhibits Esophageal Squamous Cell Carcinoma Progression by Reducing IL6 Signaling

Chen

Hsieh

et al. 2015

Molecular Cancer Therapeutics

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“…Current research suggests that vitamin D and its metabolites may reduce progression of many types of cancers [1]. Despite the large amount of recent research that has investigated the associations between vitamin D and cancer [9,10], the exact mechanism of the protective effect of vitamin D remained incompletely understood.…”

Section: Introductionmentioning

confidence: 99%

1α,25(OH)2D3 Induces Actin Depolymerization in Endometrial Carcinoma Cells by Targeting RAC1 and PAK1

Zeng

Salker

Zhang

et al. 2016

Cell Physiol Biochem

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Background: Cell proliferation and motility require actin reorganization, which is under control of various signalling pathways including ras-related C3 botulinum toxin substrate 1 (RAC1), p21 protein-activated kinase 1 (PAK1) and actin related protein 2 (ARP2). Tumour cell proliferation is modified by 1α,25-Dihydroxy-Vitamin D3 (1α,25(OH)₂D₃), a steroid hormone predominantly known for its role in calcium and phosphorus metabolism. The present study explored whether 1α,25(OH)₂D₃ modifies actin cytoskeleton in Ishikawa cells, a well differentiated endometrial carcinoma cell line. Methods: To this end, actin cytoskeleton was visualized by confocal microscopy. Globular over filamentous actin ratio was determined utilizing Western blotting and flow cytometry, transcript levels by qRT-PCR and protein abundance by immunoblotting. Results: A 24 hour treatment with 1α,25(OH)₂D₃ (100 nM) significantly decreased RAC1 and PAK1 transcript levels and activity, decreased ARP2 protein levels and depolymerized actin. The effect of 1α,25(OH)₂D₃ on actin polymerization was mimicked by pharmacological inhibition of RAC1 and PAK1. Conclusions: 1α,25(OH)₂D₃ leads to disruption of RAC1 and PAK1 activity with subsequent actin depolymerization of endometrial carcinoma cells.

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“…There is a growing body of epidemiologic and laboratory evidence in support of vitamin D for the prevention of a number of malignancies including endometrial cancer (14,15). Vitamin D3, produced in the epidermis or obtained from the diet, is metabolized to the dihydroxylated form [calcitriol, 1,25-(OH) 2 D 3 ] to be biologically active.…”

Section: Introductionmentioning

confidence: 99%

“…The inhibitory role of calcitriol in cellular growth and proliferation potentially provides protection from various types of cancers, as indicated by several epidemiologic studies (19,20). However, as calcitriol has been found to be efficacious in several preclinical and clinical studies, dose-limiting calcemic effects have proved a major obstacle for the use of this compound as a chemotherapeutic or chemopreventive agent (14,15). One approach to limit the toxicity is to use lower concentrations of calcitriol in combination with other agents that enhance its anticancer activity.…”

Section: Introductionmentioning

confidence: 99%

Progesterone Enhances Calcitriol Antitumor Activity by Upregulating Vitamin D Receptor Expression and Promoting Apoptosis in Endometrial Cancer Cells

Lee

Teng

Nguyen

et al. 2013

Cancer Prevention Research

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Human studies suggest that progesterone and calcitriol may prove beneficial in preventing or inhibiting oncogenesis, but the underlying mechanism is not fully understood. The current study investigates the effects of progesterone, calcitriol, and their combination on immortalized human endometrial epithelial cells and endometrial cancer cells and identifies their targets of action. Combination treatment with both agents enhanced vitamin D receptor expression and inhibited cell proliferation through caspase-3 activation and induction of G 0 -G 1 cell-cycle arrest with associated downregulation of cyclins D1 and D3 and p27 induction. We used mass spectrometry-based proteomics to measure protein abundance differences between calcitriol-, progesterone-, or combination-exposed endometrial cells. A total of 117 proteins showed differential expression among these three treatments. Four proteins were then selected for validation studies: histone H1.4 (HIST1H1E), histidine triad nucleotide-binding protein 2 (HINT2), IFN-induced, double-stranded RNA-activated protein kinase (EIF2AK2), and Bcl-2-associated X protein (BAX). Abundance levels of selected candidates were low in endometrial cancer cell lines versus the immortalized endometrial epithelial cell line. All four proteins displayed elevated expression in cancer cells upon exposure to calcitriol, progesterone, or the combination. Further BAX analysis through gain-or loss-of-function experiments revealed that upregulation of BAX decreased cell proliferation by changing the BAX:BCL-2 ratio. Knockdown of BAX attenuated progesterone-and calcitriol-induced cell growth inhibition. Our results showed that progesterone and calcitriol upregulate the expression of BAX along with other apoptosis-related proteins, which induce inhibition of endometrial cancer cell growth by apoptosis and cell-cycle arrest. Cancer Prev Res; 6(7); 731-43. Ó2013 AACR.

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Current progress in using vitamin D and its analogs for cancer prevention and treatment

Cited by 38 publications

References 128 publications

1α,25-Dihydroxyvitamin D3 Inhibits Esophageal Squamous Cell Carcinoma Progression by Reducing IL6 Signaling

1α,25-Dihydroxyvitamin D3 Inhibits Esophageal Squamous Cell Carcinoma Progression by Reducing IL6 Signaling

1α,25(OH)2D3 Induces Actin Depolymerization in Endometrial Carcinoma Cells by Targeting RAC1 and PAK1

Progesterone Enhances Calcitriol Antitumor Activity by Upregulating Vitamin D Receptor Expression and Promoting Apoptosis in Endometrial Cancer Cells

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