Journal
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
Volume 13, Issue 1, Pages 20-35Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/187152013804487434
Keywords
Cancer; Vitamin D; Calcium; CYP27B1; 1 alpha-hydroxylase; CYP24A1; 24-hydroxylase; CYP27A1; CYP2R1; 25-hydroxylase; calcium sensing receptor; CaSR; colorectal cancer; Proliferation; Methylation; Epigenetics; Splice variants; COX-2; Wnt
Categories
Funding
- Austrian Research Fund (FWF) [P22200-B11]
- European Union [264663]
- DOC-fFORTE fellowship from the Austrian Academy of Science [23478]
Ask authors/readers for more resources
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, 1 alpha,25-dihydroxyvitamin D-3 (1,25-D-3). 25-hydroxylases in the liver are responsible for the first hydroxylation step. The ultimate activation is performed by the renal 25-hydroxyvitamin D 1 alpha-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-D-3 levels, and are responsible for maintaining mineral homeostasis. In addition, the active vitamin D hormone 1,25-D-3 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 D-3 (25-D-3) 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-D-3 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available