Vitamin D and vitamin D analogs in cancer treatment

The secosteroid hormone 1,25-dihydroxyvitamin D-3 (1,25-(OH)A) is a key player in the regulation of bone mineralization and calcium homeostasis. In addition, 1,25-(OH)(2)D-3 has antiproliferative and prodifferentiation effects on various cells in vitro and in vivo. The growth-inhibitory properties of 1,25-(OH)(2)D-3 could be harnessed in the treatment of cancer. However, its use as an anti-cancer drug is limited because of the calcemic effects of pharmacological doses. In an attempt to dissociate the antiproliferative and calcemic effects, numerous vitamin D3 analogs were developed. The mechanisms by which 1,25-(OH)(2)D-3 and 1,25-(OH)(2)D-3 analogs exert their growth-inhibitory effects are not clear but include effects on cell differentiation, apoptosis, cell cycle regulation, metastases, and angiogenesis. In the current review aspects involved in the tumor suppressive activity of 1,25-(OH)(2)D-3 and 1,25-(OH)(2)D-3 analogs will be addressed. The use of vitamin D-3 compounds, alone or in combination with other drugs, in cancer treatment and the potential drawbacks will also be discussed.