Unfortunately, no single agent or combination of agents administered systemically provided beneficial effects on survival rate.9,10 Recently, with the advances in understanding the molecular biology of HCC, new therapeutic strategies to treat HCC have emerged.11 For instance, the clinical efficiency of sorafenib, an oral multi-kinase inhibitor of several kinases (vascular

endothelial growth factor [VEGF], platelet-derived growth factor [PDGF], c-kit receptor, selleck compound Raf) with antiproliferative and anti-angiogenesis prosperities in HCC, has been studied in clinical trials. Although sorafenib could benefit advanced-HCC patients, the effect is rather limited.12 Vitamin D, identified as a hormone to maintain blood calcium homeostasis and promote skeletal mineralization, has been demonstrated to learn more exert additional functions, including antiproliferative, pro-differentiation, pro-apoptotic,

anti-angiogenesis and anti-invasive characteristics in many cancer cell systems during the past two decades. These antitumor activities have led to several clinical trials. Regarding HCC, vitamin D has also been investigated from in vitro, pre-clinical animal studies to clinical trials. In this review, we discussed the source and metabolism of vitamin D, a new emerging aspect of the genomic and non-genomic actions of vitamin D, vitamin D receptor (VDR) polymorphism, clinical trials and the latest development of Rucaparib mw vitamin D analogs for potential HCC therapy. There are two common forms of vitamin D: vitamin D2 and vitamin D3. They originate from two distinct sources. Vitamin D2 (ergocalciferol) is synthesized from ergosterol of yeast and vitamin D3 (cholecalciferol) is produced from 7-dehydrocholesterol (7-DHC) of lanolin. (Fig. 1). Vitamin D (representing D2 and D3) is rare in foods, only few foods contain sufficient vitamin D naturally.13 Therefore, fortification of vitamin D in foods or taking a supplement is gaining popularity

in some countries. To most humans, exposure to sunlight accounts for about 90% of vitamin D requirements.13 Vitamin D is inert biologically. Vitamin D is first hydroxylated in the liver by vitamin D-25-hydroxylase (25-OHase)14 to form 25-hydroxyvitamin D [25(OH)D], the circulating form of vitamin D. 25(OH)D is considered as the most reliable index of human vitamin D status. 25(OH)D circulates as a vitamin-D-binding-protein (DBP)-bound form in the blood stream. Upon entering the kidneys, 25(OH)D is further hydroxylated mainly in the proximal tubules at the C-1 position to form 1α,25-dihydroxyvitamin D [1α,25(OH)2D], catalyzed by 25(OH)D-1α-hydroxylase (1α-OHase or CYP27B1). Among all of the vitamin D metabolites, 1α,25(OH)2D is the most active form. Another renal enzyme that also plays a crucial role is 25(OH)D-24-hydroxylase (24-OHase or CYP24A1).