Vitamin D Research Today is a free monthly online journal that collates and summarizes the latest research about Vitamin D, including details on sources, melanin, benefits, deficiency, supplements, calcium absorption.

1alpha,25-dihydroxyvitamin D3 (Calcitriol) inhibits hypoxia-inducible factor-1/vascular endothelial growth factor pathway in human cancer cells.

Ben-Shoshan M, Amir S, Dang DT, Dang LH, Weisman Y, Mabjeesh NJ

Department of Pediatrics, Dana Children's Hospital, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.

In vitro and in vivo studies have shown that 1alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] inhibits angiogenesis in cancer. We now examined whether the antiangiogenic effects of 1,25(OH)(2)D(3) are mediated by the hypoxia-inducible factor (HIF)-1 pathway. Our results showed that 1,25(OH)(2)D(3) reduces the protein expression of both the regulated HIF-1alpha subunit and the vascular endothelial growth factor (VEGF) in various human cancer cells. 1,25(OH)(2)D(3) also inhibited HIF-1 transcriptional activity (measured by reporter gene assay) as well as HIF-1 target genes, including VEGF, ET-1, and Glut-1. We also showed that 1,25(OH)(2)D(3) inhibits cell proliferation under hypoxia. Using HIF-1alpha knockout colon cancer cells, we show that the inhibition of the hypoxia-induced VEGF by 1,25(OH)(2)D(3) is mediated through a HIF-dependent pathway. Because HIF-1 is a major positive contributor in human tumorigenesis and angiogenesis, we believe that its inhibition by 1,25(OH)(2)D(3) strengthens the rationale to use vitamin D and its low-calcemic analogues in cancer chemoprevention and therapy.

Published 13 April 2007 in Mol Cancer Ther, 6(4): 1433-9.
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