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Vitamin D and Cancer pp 1–24Cite as

Vitamin D: Synthesis and Catabolism – Considerations for Cancer Causation and Therapy

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Abstract

Protection from sporadic malignancies by vitamin D can be traced to the role of its hormonally active metabolite, 1,25-dihdroxyvitamin D3 (1,25-(OH)2D3) 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-1α-hydroxylase, the enzyme responsible for conversion of 25-(OH)D3 to 1,25-(OH)2D3. In vitamin D insufficiency, availability of 25-(OH)D3 is low, so that extrarenal CYP27B1 activity may not be high enough to achieve tissue concentrations of 1,25-(OH)2D3 necessary to control growth and prevent neoplastic transformation of colonocytes.

While adequate supply of the vitamin D precursor 25-(OH)D3 is essential for prevention of tumor progression, activity of the extrarenal synthesizing CYP27B1 is of paramount importance especially in view of the fact that 1,25-(OH)2D3 catabolism is progressively elevated during tumor progression. To counteract catabolism, enhancement of 1,25-(OH)2D3 synthesis is discussed. Early during cancer progression growth factors and sex hormones may elevate CYP27B1 expression and suppress that of CYP24A1. Also, genetic variations and epigenetic regulation of vitamin D hydroxylases could determine actual accumulation of 1,25-(OH)2D3 in 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 appropriate 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)2D3 for prevention of cancers in humans. Especially folate, as a methyl donor, could affect epigenetic regulation of CYP27B1 and of CYP24A1, and could therefore play a central role in vitamin D-mediated inhibition of tumor progression.

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  1. Department of Pathophysiology, Medical University of Vienna, Waehringer Guertel 18–20, A-1090, Vienna, Austria

    Heide S. Cross

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  1. Roswell Park Cancer Institute, Grace Cancer Drug Center, New York State Department of Health, Elm & Carlton St., Buffalo, 14263, New York, USA

    Donald L. Trump

  2. Roswell Park Cancer Institute, Grace Cancer Drug Center, New York State Department of Health, Elm & Carlton St., Buffalo, 14263, New York, USA

    Candace S. Johnson

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Cross, H.S. (2011). Vitamin D: Synthesis and Catabolism – Considerations for Cancer Causation and Therapy. In: Trump, D., Johnson, C. (eds) Vitamin D and Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-7188-3_1

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