Vitamin D and cancer:: Effects of 1,25(OH)2D3 and its analogs on growth control and tumorigenesis

Today, it is well established that besides playing a crucial role in the establishment and maintenance of the calcium homeostasis in the body, the active form of vitamin D, 1,25(OH)(2)D-3, also acts an effective regulator of cell growth and differentiation in a number of different cell types, including cancer cells. This has led to an increased interest in using 1,25(OH)(2)D-3 in the treatment or prevention of cancer patients and to a substantial number of studies investigating the effect of 1,25(OH)(2)D-3 on cancer cells. The results are encouraging, but clearly demonstrate that the therapeutic window of 1,25(OH)(2)D-3 is extremely narrow due to the calcemic adverse effects of this compound. Much effort has consequently been directed into identifying vitamin D analogs with potent cell regulatory effects but with weaker effects on the calcium metabolism than those of 1,25(OH)(2)D-3. In an attempt to clarify the mechanisms implicated in the cell regulatory effects of 1,25(OH)(2)D-3 and eventually facilitate the process of developing new specific vitamin D analogs, numerous investigations have been carried out with 1,25(OH)(2)D-3 and its analogs. The present review will focus on the results obtained in these studies and describe some of the synthetic analogs, which have shown to be of particular interest in relation to cancer.