Vitamin d in the prevention, development and therapy of oncological diseases,

Vitamin D, traditionally known as a fat-soluble essential vitamin, is a precursor of a powerful steroid hormone that regulates a broad spectrum of physiological processes. In addition to its fundamental role in bone metabolism, epidemiological, preclinical and cellular researches in recent decades have revealed that vitamin D can play a considerable role in the prevention of some pathologies, including extra-skeletal ones, such as neoplasms. Vitamin D, as a prohormone, undergoes first hepatic and subsequently renal metabolism to produce a biologically active metabolite, calcitriol or 1α,25-dihydroxyvitamin D or (1,25 (OH)2D), which binds the vitamin D receptor by regulating the expression of several genes involved in bone metabolism and other biological functions. Furthermore, recent studies have revealed that vitamin D can be also metabolized and activated through a non-canonical metabolic pathway catalyzed by CYP11A1, the gene encoding the cholesterol side chain cleavage enzyme or P450scc. The metabolites of vitamin D deriving from the CYP11A1 enzyme have shown antiproliferative and anti-inflammatory activities and are able to promote the differentiation process on neoplastic cells in comparable way or better than calcitriol, thus contributing to its tumor preventive effect. Clinical data have demonstrated that vitamin D has anticancer activity against prostate, colon, and breast cancers. Several molecular mechanisms of vitamin D involved in tumor etiopathogenesis have been proposed that have not yet been fully clarified. Vitamin D may play a key role in preventing the early stage of the neoplastic process by exerting anti-inflammatory, antioxidant defenses and inducing enzymes responsible for repairing DNA damage and could also be involved in mechanisms of inhibition of cell proliferation, induction of cell differentiation, and cell death. In addition, some studies indicate various mechanisms through which vitamin D can quantitatively and qualitatively influence the intestinal microbiota, strongly linked to chronic inflammatory bowel diseases and the development of colon cancer. However, the metabolism and functions of vitamin D are dysregulated in some neoplasms which therefore develop resistance to the antiproliferative effect of vitamin D, and this promotes tumor development and progression. In this review, studies regarding vitamin D in relation to its activity in cancer have been summarized, as long as the metabolic pathways described for vitamin D.