Role of Calcium, Vitamin D, and the Extrarenal Vitamin D Hydroxylases in Carcinogenesis

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)

Volume 16, 12 Issues, 2016

Download PDF Flyer

Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

Aims & ScopeAbstracted/Indexed in

Ranking and Category:
  • 27th of 59 in Chemistry, Medicinal

Submit Abstracts Online Submit Manuscripts Online

Michelle Prudhomme
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex

View Full Editorial Board

Subscribe Purchase Articles Order Reprints

Current: 2.722
5 - Year: 2.849

Role of Calcium, Vitamin D, and the Extrarenal Vitamin D Hydroxylases in Carcinogenesis

Anti-Cancer Agents in Medicinal Chemistry, 13(1): 20-35.

Author(s): Julia Hobaus, Ursula Thiem, Doris M. Hummel and Eniko Kallay.

Affiliation: Department of Pathophysiology and Allergy Research, Medical university of Vienna, Wahringer Gurtel 18- 20, AKH, Leitstelle 3Q, A-1090, Vienna, Austria.


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.


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.

Download Free Order Reprints Order Eprints Rights and Permissions

Article Details

Volume: 13
Issue Number: 1
First Page: 20
Last Page: 35
Page Count: 16
DOI: 10.2174/1871520611307010020

Related Journals

Webmaster Contact: Copyright © 2016 Bentham Science