Vitamin D Compounds: Activity Against Microbes and Cancer

Abstract

Vitamin D₃ is produced in skin and is sequentially metabolized by the liver and kidney to the biologically active form 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃]. It is a seco-steroid hormone that regulates calcium homeostasis within the body. The genomic actions of 1,25(OH)₂D₃ are modulated through the vitamin D receptor (VDR) (1). VDR belongs to a superfamily of nuclear receptors that transduce hormonal signals from the immediate environment and transactivate genes in response to these signals. Target genes contain hormone response elements (VDREs) in their promoters to which heterodimers of VDR and retinoid X receptors (RXR) can bind and transactivate expression of the target genes (2). The VDR is expressed in at least 30 different target tissues including bone, kidney, blood, breast, prostate, gut, activated B- and T-lymphocytes, monocytes and keratinocytes (3, 4). Most dividing cell types, normal and malignant, can express VDR and respond to 1,25(OH)₂D₃. Although 1,25(OH)₂D₃ and its analogs (termed deltanoids) are important regulators of calcium and bone metabolism, their non-calciotropic activities that include inhibition of cell proliferation, promotion of cell differentiation and modulation of immune cell function have spurred interest in therapeutic applications in a wide variety of diseases. In this report, the anticancer and newly discovered antimicrobial actions of 1,25(OH)₂D₃ and deltanoids are reviewed.