Vitamin D signalling pathways in cancer: potential for anticancer therapeutics

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FIGURE 1 | Vitamin D metabolism.

From the following article:

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Vitamin D signalling pathways in cancer: potential for anticancer therapeutics

Kristin K. Deeb, Donald L. Trump & Candace S. Johnson

Nature Reviews Cancer 7, 684-700 (September 2007)

doi:10.1038/nrc2196

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Photochemical synthesis of vitamin D3 (cholecalciferol, D3) occurs cutaneously where pro-vitamin D3 (7-dehydrocholesterol) is converted to pre-vitamin D3 (pre-D3) in response to ultraviolet B (sunlight) exposure. Vitamin D3, obtained from the isomerization of pre-vitamin D3 in the epidermal basal layers or intestinal absorption of natural and fortified foods and supplements, binds to vitamin D-binding protein (DBP) in the bloodstream, and is transported to the liver. D3 is hydroxylated by liver 25-hydroxylases (25-OHase). The resultant 25-hydroxycholecalciferol (25(OH)D3) is 1-hydroxylated in the kidney by 25-hydroxyvitamin D3-1-hydroxylase (1-OHase). This yields the active secosteroid 1,25(OH)2D3 (calcitriol), which has different effects on various target tissues23. The synthesis of 1,25(OH)2D3 from 25(OH)D3 is stimulated by parathyroid hormone (PTH) and suppressed by Ca2+, Pi and 1,25(OH)2D3 itself. The rate-limiting step in catabolism is the degradation of 25(OH)D3 and 1,25(OH)2D3 to 24,25(OH)D3 and 1,24,25(OH)2D3, respectively,which occurs through 24-hydroxylation by 25-hydroxyvitamin D 24-hydroxylase (24-OHase), encoded by the CYP24A1 gene. 24,25(OH)D3 and 1,24,25(OH)2D3 are consequently excreted. The main effects of 1,25(OH)2D3 on various target tissues are highlighted above.

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  • Nature Reviews Cancer

  • ISSN: 1474-175X

  • EISSN: 1474-1768

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