Potent 19-norvitamin D analogs for prostate and liver cancer therapy

The active form of vitamin D₃, 1α,25(OH)₂D ₃ or calcitriol, is known to inhibit the proliferation and invasiveness of many types of cancer cells, including prostate and liver cancer cells. These findings support the use of 1α,25(OH)₂D ₃ for prostate and liver cancer therapy. However, 1α,25(OH)₂D₃ can cause hypercalcemia, thus, analogs of 1α,25(OH)₂D₃ that are less calcemic but exhibit potent antiproliferative activity would be attractive as therapeutic agents. We have developed 2α-functional group substituted 19-norvitamin D₃ analogs with and without 14-epimerization. Among them, 2α- and 2β-(3-hydroxypropyl)-1α,25-dihydroxy-19-norvitamin D₃ (MART-10 and -11, respectively) and 14-epi-2α- and 14-epi-2β-(3- hydroxypropyl)-1α,25-dihydroxy-19-norvitamin D₃ (14-epi-MART-10 and 14-epi-MART-11, respectively) were found to be the most promising. In this review, we discuss the synthesis of this unique class of vitamin D analogs, the molecular mechanism of anticancer actions of vitamin D, and the biological evaluation of these analogs for potential application to the prevention and treatment of prostate and liver cancer.