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 (1α-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 μg/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(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.