Abstract
Vitamin D deficiency and low calcium intake are considered risk factors for several cancers. Vitamin D, synthesized in the skin or ingested through the diet, is transformed through two hydroxylation steps to the active metabolite, 1α,25-dihydroxyvitamin D3 (1,25-D3). 25-hydroxylases in the liver are responsible for the first hydroxylation step. The ultimate activation is performed by the renal 25-hydroxyvitamin D 1α-hydroxylase (CYP27B1), while the 1,25-dihydroxyvitamin D 24-hydroxylase (CYP24A1) in the kidneys degrades the active metabolite. These two renal vitamin D hydroxylases control the endocrine serum 1,25-D3 levels, and are responsible for maintaining mineral homeostasis. In addition, the active vitamin D hormone 1,25-D3 regulates cellular proliferation, differentiation, and apoptosis in multiple tissues in a paracrine/autocrine manner. Interestingly, it is the low serum level of the precursor 25- hydroxyvitamin D3 (25-D3) that predisposes to numerous cancers and other chronic diseases, and not the serum concentration of the active vitamin D hormone. The extra-renal autocrine/paracrine vitamin D system is able to synthesize and degrade locally the active 1,25- D3 necessary to maintain normal cell growth and to counteract mitogenic stimuli. Thus, vitamin D hydroxylases play a prominent role in this process.
The present review describes the role of the vitamin D hydroxylases in cancer pathogenesis and the cross-talk between the extra-renal autocrine/paracrine vitamin D system and calcium in cancer prevention.
Keywords: Cancer, Vitamin D, Calcium, CYP27B1, 1α-hydroxylase, CYP24A1, 24-hydroxylase, CYP27A1, CYP2R1, 25-hydroxylase, calcium sensing receptor, CaSR, colorectal cancer, Proliferation, Methylation, Epigenetics, Splice variants, COX-2, Wnt
Anti-Cancer Agents in Medicinal Chemistry
Title:Role of Calcium, Vitamin D, and the Extrarenal Vitamin D Hydroxylases in Carcinogenesis
Volume: 13 Issue: 1
Author(s): Julia Hobaus, Ursula Thiem, Doris M. Hummel and Eniko Kallay
Affiliation:
Keywords: Cancer, Vitamin D, Calcium, CYP27B1, 1α-hydroxylase, CYP24A1, 24-hydroxylase, CYP27A1, CYP2R1, 25-hydroxylase, calcium sensing receptor, CaSR, colorectal cancer, Proliferation, Methylation, Epigenetics, Splice variants, COX-2, Wnt
Abstract: Vitamin D deficiency and low calcium intake are considered risk factors for several cancers. Vitamin D, synthesized in the skin or ingested through the diet, is transformed through two hydroxylation steps to the active metabolite, 1α,25-dihydroxyvitamin D3 (1,25-D3). 25-hydroxylases in the liver are responsible for the first hydroxylation step. The ultimate activation is performed by the renal 25-hydroxyvitamin D 1α-hydroxylase (CYP27B1), while the 1,25-dihydroxyvitamin D 24-hydroxylase (CYP24A1) in the kidneys degrades the active metabolite. These two renal vitamin D hydroxylases control the endocrine serum 1,25-D3 levels, and are responsible for maintaining mineral homeostasis. In addition, the active vitamin D hormone 1,25-D3 regulates cellular proliferation, differentiation, and apoptosis in multiple tissues in a paracrine/autocrine manner. Interestingly, it is the low serum level of the precursor 25- hydroxyvitamin D3 (25-D3) that predisposes to numerous cancers and other chronic diseases, and not the serum concentration of the active vitamin D hormone. The extra-renal autocrine/paracrine vitamin D system is able to synthesize and degrade locally the active 1,25- D3 necessary to maintain normal cell growth and to counteract mitogenic stimuli. Thus, vitamin D hydroxylases play a prominent role in this process.
The present review describes the role of the vitamin D hydroxylases in cancer pathogenesis and the cross-talk between the extra-renal autocrine/paracrine vitamin D system and calcium in cancer prevention.
Export Options
About this article
Cite this article as:
Hobaus Julia, Thiem Ursula, M. Hummel Doris and Kallay Eniko, Role of Calcium, Vitamin D, and the Extrarenal Vitamin D Hydroxylases in Carcinogenesis, Anti-Cancer Agents in Medicinal Chemistry 2013; 13 (1) . https://dx.doi.org/10.2174/1871520611307010020
DOI https://dx.doi.org/10.2174/1871520611307010020 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Stem Cells, Cancer, Liver, and Liver Cancer Stem Cells: Finding a Way Out of the Labyrinth...
Current Cancer Drug Targets Safety of Technosphere Inhaled Insulin
Current Drug Safety Possible Molecular Mechanisms by which Vitamin D Prevents Inflammatory Bowel Disease and Colitis-associated Colorectal Cancer
Current Medicinal Chemistry Inhibition of TGF-β Signaling in Tumor Cells by Small Molecule Src Family Kinase Inhibitors
Anti-Cancer Agents in Medicinal Chemistry Novel Strategies of Regenerative Medicine Using Chemical Compounds
Current Medicinal Chemistry It Takes Two to Tango: The Structure and Function of LIM, RING, PHD and MYND Domains
Current Pharmaceutical Design Cancer Stem Cell Model in Oral Squamous Cell Carcinoma
Current Stem Cell Research & Therapy Cytoprotection and Immunomodulation in Cancer Therapy
Current Medicinal Chemistry - Anti-Cancer Agents HPV Infections: Basis of Neoplastic Transformation and Related Molecular Tests
Current Pharmaceutical Design Phosphorothioate-Stimulated Uptake of siRNA by Mammalian Cells: A Novel Route for Delivery
Current Topics in Medicinal Chemistry Peripheral Benzodiazepine Receptor (PBR) New Insight in Cell Proliferation and Cell Differentiation Review
Current Clinical Pharmacology Chemical and physical factors influencing the dynamics of differentiation in embryonic stem cells
Current Stem Cell Research & Therapy Role of Chemokines and Their Receptors in Cancer
Current Pharmaceutical Design The Epithelial-Mesenchymal Transition and Cancer Stem Cells: Functional and Mechanistic Links
Current Pharmaceutical Design Gonadotropin-Releasing Hormone Receptor System: Modulatory Role in Aging and Neurodegeneration
CNS & Neurological Disorders - Drug Targets A Genetic Dissection of Antipsychotic Induced Movement Disorders
Current Medicinal Chemistry Combined Chemotherapy or Biotherapy with Jasmonates: Targeting Energy Metabolism for Cancer Treatment
Current Pharmaceutical Biotechnology Current State of ERG as Biomarker in Prostatic Adenocarcinoma
Current Cancer Drug Targets Inhibitors of the Ubiquitin-Proteasome System and the Cell Death Machinery: How Many Pathways are Activated?
Current Molecular Pharmacology Natural and Synthetic Retinoids: Structural Bases and Biological Effects of Potential Clinical Relevance for the Prevention and Treatment of Infection-Driven Tumors
Anti-Infective Agents in Medicinal Chemistry