Novel Vitamin D Analogs for Prostate Cancer Therapy

Figure 7

Metabolism and the nonclassical actions of vitamin D in prostate cells. Prostate cells express vitamin D 25-hydroxylase (25-OHase, or CYP2R1, a microsomal enzyme), 1α-OHase (or CYP27B1, a mitochondrial enzyme), and 24-OHase (or CYP24A1, a mitochondrial enzyme) and, therefore, are capable of synthesizing 1𝛼,25(OH)₂D₃ from vitamin D₃. Binding of 1𝛼,25(OH)₂D₃ or 25(OH)D₃ to the vitamin D receptor (VDR) causes the VDR to heterodimerize with the retinoid X receptor (RXR). The VDR-RXR heterodimer binds to specific vitamin D response elements in the promoter region of vitamin-D-responsive genes and induces gene transcription. The gene products include proteins involved in its own metabolism (CYP24A1), cell-cycle arrest, apoptosis, differentiation, anti-invasion, antiangiogenesis, and many other actions.