The role of vitamin D3 in signaling pathways – potential anticancer properties of calcitriol and its analogues

Vitamin D, for many years after the discovery, primarily was associated with bone metabolic processes. Currently, many studies indicate its beneficial effect in the prevention and treatment of many diseases, including cancer. However, deficiency of vitamin D is associated with greater tendency to get sick and worse prognosis in treatment, especially cancer. Calcitriol, an active form of vitamin D (1.25(OH)2D3) and its analogues have a pleiotropic activity, including anti-cancer properties. Many studies indicate, that the active forms of vitamin D3 may show anti-proliferative effects in cancer cells by inhibiting the cell cycle, inducing differentiation orleading to apoptosis and enhancing autophagy. Also, extremely important are the possibilitiesof reducing the invasiveness of tumours through the influence on angiogenesis or adhesion andothers. Especially, the anti-cancer role of vitamin D3 is suggested in the case of tumors whose cellsexpress VDR receptors. Interestingly, many cancer cells not only express the VDR receptors, butalso due to the expression of CYP27B1 and CYP24A hydroxylases, they can regulate metabolismof calcitriol. Many of the studies using vitamin D3 show that calcitriol and its analogues, dueto the influence on cancer cells, can play promising roles in anticancer therapies. Consider thebroad pleiotropism of the action of active metabolites of vitamin D3 and the development ofresearch in this field, the current work presents the effect of active forms of vitamin D on somesignalling pathways and the regulation of selected proteins in various cancers.