Induction of Differentiation in Cancer Cells by Vitamin D: Recognition and Mechanisms

The human ether à go-go 1 potassium channel (hEAG1) is required for cell cycle progression and proliferation of cancer cells. Inhibitors of hEAG1 activity and expression represent potential therapeutic drugs in cancer. Previously, we have shown that hEAG1 expression is downregulated by calcitriol in a variety of cancer cells. Herein, we provided evidence on the regulatory mechanism involved in such repressive effect in cells derived from human cervical cancer. Our results indicate that repression by calcitriol occurs at the transcriptional level and involves a functional negative vitamin D response element (nVDRE) E-box type in the hEAG1 promoter. The described mechanism in this work implies that a protein complex formed by the vitamin D receptor-interacting repressor, the vitamin D receptor, the retinoid X receptor, and the Williams syndrome transcription factor interact with the nVDRE in the hEAG1 promoter in the absence of ligand. Interestingly, all of these transcription factors except the vitamin D receptor-interacting repressor are displaced from hEAG1 promoter in the presence of calcitriol. Our results provide novel mechanistic insights into calcitriol mode of action in repressing hEAG1 gene expression.

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MicroRNA-22 is induced by vitamin D and contributes to its antiproliferative, antimigratory and gene regulatory effects in colon cancer cells

Human Molecular Genetics ◽

10.1093/hmg/dds031 ◽

2012 ◽

Vol 21 (10) ◽

pp. 2157-2165 ◽

Cited By ~ 95

Author(s):

Silvia Alvarez-Díaz ◽

Noelia Valle ◽

Gemma Ferrer-Mayorga ◽

Luis Lombardía ◽

Mercedes Herrera ◽

...

Keyword(s):

Colon Cancer ◽

Vitamin D ◽

Cancer Cells ◽

Colon Cancer Cells ◽

Gene Regulatory ◽

Regulatory Effects

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VITAMIN D DERIVATIVES IN COMBINATION WITH 9-cis RETINOIC ACID PROMOTE ACTIVE CELL DEATH IN BREAST CANCER CELLS

Journal of Molecular Endocrinology ◽

10.1677/jme.0.0140391 ◽

1995 ◽

Vol 14 (3) ◽

pp. 391-394 ◽

Cited By ~ 53

Author(s):

S Y James ◽

A G Mackay ◽

K W Colston

Keyword(s):

Breast Cancer ◽

Vitamin D ◽

Retinoic Acid ◽

Cancer Cells ◽

Breast Cancer Cells ◽

P53 Protein ◽

Protein A ◽

Therapeutic Implications ◽

Protein Levels ◽

Mcf 7

ABSTRACT The effects of the novel vitamin D analogue, EB1089 alone, or in combination with the retinoid, 9-cis retinoic acid (9-cis RA) on indices of apoptosis in MCF-7 breast cancer cells have been examined. EB1089 was capable of reducing bcl-2 protein, a suppressor of apoptosis, and increasing p53 protein levels in MCF-7 cell cultures following 96h treatment. In the presence of 9-cis RA, EB1089 acted to further enhance the down-regulation and up-regulation of bcl-2 and p53 respectively. Furthermore, EB1089 induces DNA fragmentation in MCF-7 cells, a key feature of apoptosis, alone and in combination with 9-cis RA in situ. The observation that EB1089 and 9-cis RA act in a cooperative manner to enhance induction of apoptosis in these cells may have therapeutic implications.

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Nuclear Vitamin D (VDR) and Estrogen (ER) Receptors in the Membrane of Muscle and Breast Cancer Cells

The Identities of Membrane Steroid Receptors ◽

10.1007/978-1-4615-0339-2_7 ◽

2003 ◽

pp. 57-65

Author(s):

Daniela Capiati ◽

Graciela Santillán ◽

Ana Rossi ◽

Paula Monje ◽

Ricardo Boland

Keyword(s):

Breast Cancer ◽

Vitamin D ◽

Cancer Cells ◽

Breast Cancer Cells

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Role of Rb Family in Vitamin D Receptor-Mediated Anti-Tumor Effects in Ovarian Cancer Cells.

10.1210/endo-meetings.2010.part1.p1.p1-9 ◽

2010 ◽

pp. P1-9-P1-9

Author(s):

J Tang ◽

P Li ◽

AKW Tse ◽

SV Nicosia ◽

X Zhang ◽

...

Keyword(s):

Ovarian Cancer ◽

Vitamin D ◽

Cancer Cells ◽

Vitamin D Receptor ◽

Ovarian Cancer Cells

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25-Hydroxy-Vitamin D Metabolism in Human Colon Cancer Cells during Tumor Progression

Biochemical and Biophysical Research Communications ◽

10.1006/bbrc.2001.5289 ◽

2001 ◽

Vol 285 (4) ◽

pp. 1012-1017 ◽

Cited By ~ 103

Author(s):

Petra Bareis ◽

Giovanna Bises ◽

Martin G. Bischof ◽

Heide S. Cross ◽

Meinrad Peterlik

Keyword(s):

Colon Cancer ◽

Vitamin D ◽

Tumor Progression ◽

Cancer Cells ◽

Human Colon ◽

Colon Cancer Cells ◽

Human Colon Cancer ◽

Vitamin D Metabolism ◽

25 Hydroxy Vitamin D ◽

Human Colon Cancer Cells

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The Role of Vitamin D and the Vitamin D Receptor in Bone Oncology

Osteologie/Osteology ◽

10.1055/s-0038-1673534 ◽

2018 ◽

Vol 27 (03) ◽

pp. 129-134 ◽

Cited By ~ 1

Author(s):

B. M. Holzapfel ◽

F. Jakob ◽

A. A. Kurth ◽

G. Maier ◽

K. Horas

Keyword(s):

Vitamin D ◽

Cancer Cells ◽

Vitamin D Deficiency ◽

Vitamin D Receptor ◽

Molecular Mechanisms ◽

Full Range ◽

Cancer Cell Growth ◽

The Past ◽

Global Health Problem

SummaryVitamin D deficiency is a global health problem of enormous and increasing dimensions. In the past decades, numerous studies have centered on the role of vitamin D in the pathogenesis and course of many diseases including several types of cancer. Indeed, vitamin D has been widely acknowledged to be involved in the regulation of cell proliferation, differentiation and apoptosis in numerous cancer cells. While the full range of molecular mechanisms involveld in cancer cell growth and progression remains to be elucidated, recent research has deepened our understanding of the processes that may be affected by vitamin D or vitamin D deficiency.In this review, we consider the properties of bone that enable cancer cells to grow and thrive within the skeleton, and the role of vitamin D and the vitamin D receptor in the process of primary and secondary cancer growth in bone.

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High concentration calcitriol induces endoplasmic reticulum stress related gene profile in breast cancer cells

Biochemistry and Cell Biology ◽

10.1139/bcb-2016-0037 ◽

2017 ◽

Vol 95 (2) ◽

pp. 289-294 ◽

Cited By ~ 7

Author(s):

Ali Burak Ozkaya ◽

Handan Ak ◽

Hikmet Hakan Aydin

Keyword(s):

Breast Cancer ◽

Vitamin D ◽

Endoplasmic Reticulum ◽

Er Stress ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Survival Function ◽

Active Form ◽

Breast Cancer Cell Lines ◽

Transcriptomic Profile

Calcitriol, the active form of vitamin D, is known for its anticancer properties including induction of apoptosis as well as the inhibition of angiogenesis and metastasis. Understanding the mechanisms of action for calcitriol will help with the development of novel treatment strategies. Since vitamin D exerts its cellular actions via binding to its receptor and by altering expressions of a set of genes, we aimed to evaluate the effect of calcitriol on transcriptomic profile of breast cancer cells. We previously demonstrated that calcitriol alters endoplasmic reticulum (ER) stress markers, therefore in this study we have focused on ER-stress-related genes to reveal calcitriols action on these genes in particular. We have treated breast cancer cell lines MCF-7 and MDA-MB-231 with previously determined IC50 concentrations of calcitriol and evaluated the transcriptomic alterations via microarray. During analysis, only genes altered by at least 2-fold with a P value < 0.05 were taken into consideration. Our findings revealed an ER-stress-associated transcriptomic profile induced by calcitriol. Induced genes include genes with a pro-survival function (NUPR1, DNAJB9, HMOX1, LCN2, and LAMP3) and with a pro-death function (CHOP (DDIT3), DDIT4, NDGR1, NOXA, and CLGN). These results suggest that calcitriol induces an ER-stress-like response inducing both pro-survival and pro-death transcripts in the process.

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