Dietary vitamin D 3and 1,25-dihydroxyvitamin D 3 (calcitriol) exhibit equivalent anticancer activity in mouse xenograft models of breast and prostate cancer

Abstract

1,25-dihydroxyvitamin D 3 [1,25(OH) 2D 3 or calcitriol], the hormonally active vitamin D metabolite, exhibits anticancer actions in models of breast cancer and prostate cancer. Because CYP27B1 (1α-hydroxylase), the enzyme catalyzing 1,25(OH) 2D 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) 2D 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 0.1μg/mouse, three times a week). Both treatments equivalently inhibited PC-3 prostate cancer xenograft growth but to a lesser extent than the MCF-7 tumors. Calcitriol at 0.05 μg and 0.1 μg 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 dihydroxyvitamin D 3. Both calcitriol and dietary vitamin D 3were 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. Copyright © 2012 by The Endocrine Society.