Page 14 - Vitamin D and Cancer

Chapter 1
Vitamin D: Synthesis and Catabolism
– Considerations for Cancer Causation

and Therapy

Heide S. Cross

Abstract Protection from sporadic malignancies by vitamin D can be traced to the
role of its hormonally active metabolite, 1,25-dihdroxyvitamin D (1,25-(OH) D )
3
2
3
which, by binding to the nuclear vitamin D receptor (VDR), can maintain cellular
homeostasis. Human colonic, prostatic, and breast cells express the CYP27B1-
encoded 25-(OH)D-1a-hydroxylase, the enzyme responsible for conversion of
25-(OH)D to 1,25-(OH) D . In vitamin D insufficiency, availability of 25-(OH)
3
2
3
D is low, so that extrarenal CYP27B1 activity may not be high enough to achieve
3
tissue concentrations of 1,25-(OH) D necessary to control growth and prevent
3
2
neoplastic transformation of colonocytes.
While adequate supply of the vitamin D precursor 25-(OH)D is essential for
3
prevention of tumor progression, activity of the extrarenal synthesizing CYP27B1
is of paramount importance especially in view of the fact that 1,25-(OH) D catabo-
3
2
lism is progressively elevated during tumor progression. To counteract catabolism,
enhancement of 1,25-(OH) D synthesis is discussed. Early during cancer progres-
2
3
sion growth factors and sex hormones may elevate CYP27B1 expression and sup-
press that of CYP24A1. Also, genetic variations and epigenetic regulation of
vitamin D hydroxylases could determine actual accumulation of 1,25-(OH) D in
3
2
mammary, prostate, and colonic tissue and are considered both for prevention of
progression as well as for potential therapy.
Primarily in the colon as part of the digestive system, the chemopreventive
potential of vitamin D can also be augmented by nutrient factors that induce appro-
priate changes in CYP27B1 and/or CYP24A1 expression. Among these factors are
calcium, the phytoestrogen genistein and potentially also folate. Adequate intake
levels of these nutrients could augment effectiveness of 1,25-(OH) D for preven-
2
3
tion of cancers in humans. Especially folate, as a methyl donor, could affect epige-
netic regulation of CYP27B1 and of CYP24A1, and could therefore play a central
role in vitamin D-mediated inhibition of tumor progression.
H.S. Cross (*)
Department of Pathophysiology, Medical University of Vienna,
Waehringer Guertel 18–20, A-1090 Vienna, Austria
e-mail: heide.cross@meduniwien.ac.at

D.L. Trump and C.S. Johnson (eds.), Vitamin D and Cancer, 1
DOI 10.1007/978-1-4419-7188-3_1, © Springer Science+Business Media, LLC 2011