Toward Therapeutic Intervention of Cancer by Vitamin D Compounds

Extract

One area of cancer chemoprevention that has been intensively studied in recent years is biologic modifiers of cancer cells that are designed to retard proliferation ( 1 – 3 ), to induce differentiation of these cells to a quiescent, nondividing stage ( 4 ), and/or to promote cell death ( 5 – 8 ). In this issue of the Journal, Mehta et al. ( 9 ) report the effect of a novel vitamin D compound in a murine mammary gland chemoprevention model. The secosteroid hormone known as 1α,25-dihydroxyvitamin D ₃ [1α,25(OH) ₂ D ₃ ] has been described as a key regulator of serum calcium. In the last two decades, however, it has also been found to have diverse biologic effects in normal and malignant tissues. These responses include the in vitro inhibition of proliferation and induction of differentiation of various cancer cells, such as those from the human hematopoietic system, breast, ovaries, colon, brain, and prostate ( 10 – 17 ). Initiation of these genomic responses is through a specific steroid hormone nuclear vitamin D ₃ receptor (VDR) acting as a ligand-inducible transcription factor that binds the vitamin D ₃ response element contained within the promoter/enhancer region of target genes ( 18 ).