Journal
ENDOCRINOLOGY
Volume 153, Issue 6, Pages 2576-2587Publisher
OXFORD UNIV PRESS INC
DOI: 10.1210/en.2011-1600
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Funding
- National Cancer Institute [CA130991]
- Komen Foundation [070101]
- NCI [CA130991]
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1,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3 or calcitriol], the hormonally active vitamin D metabolite, exhibits anticancer actions in models of breast cancer and prostate cancer. Because CYP27B1 (1 alpha-hydroxylase), the enzyme catalyzing 1,25(OH)(2)D-3 formation in the kidney, is also expressed in extrarenal tissues, we hypothesize that dietary vitamin D-3 will be converted to 25(OH)D-3 in the body and then to 1,25(OH)(2)D-3 locally in the cancer microenvironment in which it will exert autocrine/paracrine anticancer actions. Immunocompromised mice bearing MCF-7 breast cancer xenografts showed significant tumor shrinkage (>50%) after ingestion of a vitamin D-3-supplemented diet (5000 IU/kg) compared with a control diet (1000 IU/kg). Dietary vitamin D-3 inhibition of tumor growth was equivalent to administered calcitriol (0.025, 0.05, or 0.1 mu g/mouse, three times a week). Both treatments equivalently inhibitedPC-3prostate cancerxenograftgrowthbuttoalesser extentthantheMCF-7tumors. Calcitriol at 0.05 mu g and 0.1 mu g caused modest but statistically significant increases in serum calcium levels indicating that the dietary vitamin D-3 comparison was to a maximally safe calcitriol dose. Dietary vitamin D-3 did not increase serum calcium, demonstrating its safety at the concentration tested. The vitamin D-3 diet raised circulating 1,25 dihydroxyvitamin D levels and did not alter CYP27B1 mRNA in the kidney but increased it in the tumors, suggesting that extrarenal sources including the tumors contributed to the elevated circulating 1,25 dihydroxyvitaminD(3). Both calcitriol and dietary vitamin D-3 were equipotent in suppressing estrogen synthesis and signaling and other proinflammatory and growth signaling pathways. These preclinical data demonstrate the potential utility of dietary vitamin D-3 supplementation in cancer prevention and therapy. (Endocrinology 153: 2576-2587, 2012)
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