Figure 7.

1,25(OH)₂D₃-induced signaling pathways involved in the regulation of cell proliferation, apoptosis, and inflammation in cancer. 1,25(OH)₂D₃ hampers the transition from the G₁ to the S phase of the cell cycle either directly, through upregulation of different cyclin-dependent kinase inhibitors, or indirectly through the induction of other growth factors (e.g., TGF-β, EGF). In addition, 1,25(OH)₂D₃ induces apoptosis through activation of the intrinsic apoptotic pathway or by interference with other signaling pathways such as TNF-α, EGF, β-catenin, and prostaglandins. 1,25(OH)₂D₃ has also an immunosuppressive activity, as indicated by the repression of NFκB-mediated gene transcription, which results in a suppressed production of inflammatory cytokines, such as IL-1, IL-6, IL-8, and TNF-α.