Vitamin D and cancer: Effects of 1,25(OH)(2)D-3 and its analogs on growth control and tumorigenesis

Today, it is well established that besides playing a crucial role in the es tablishment and maintenance of the calcium homeostasis in the body, the act ive 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, includ ing 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 cel ls. The results are encouraging, but clearly demonstrate that the therapeut ic 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 a n attempt to clarify the mechanisms implicated in the cell regulatory effec ts of 1,25(OH)(2)D-3 and eventually facilitate the process of developing ne w 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 analog s, which have shown to be of particular interest in relation to cancer.