The role of vitamin D in prostate cancer

Prostate cancer is the second leading cause of cancer deaths in men in the United States. Developing new treatment strategies is critical to improving the health of men. This article will be a general review of the field with a focus on research from our laboratory. Our research has focused on four areas in which we have pursued the possible use of 1 alpha ,25(OH)(2)D-3 an d its analogs to treat prostate cancer: 1) The ability of 1 alpha ,25(OH)(2)D-3 to up-regulate androgen receptors i n L.NCaP human prostate cancer cells. The implications of this finding on 1 alpha ,25(OH)(2)D-3's ability to inhibit cell growth in vivo are unclear a t present. 2) The reasons for an inability of 1 alpha ,25(OH)(2)D-3 to inhibit DU 145 prostate cancer cell growth were explored. We found that combination of an imidazole drug, Liarozole, with 1 alpha ,25(OH)(2)D-3 was capable of inhibi ting DU 145 cell growth. 3) A number of low-calcemic vitamin D analogs exhibit potent anti-prolifera tive activity on prostate cancer cells. We have developed a novel approach using the yeast two-hybrid system to screen for potent analogs. 4) The results of a clinical trial of 1 alpha ,25(OH)(2)D-3 treatment of pa tients with early recurrent prostate cancer. We provide preliminary evidenc e that 1 alpha ,25(OH)(2)D-3 may be effective in slowing the rate of PSA ri se in selected cases of prostate cancer. In conclusion, we believe that 1 alpha ,25(OH)(2)D-3, has a role in the tre atment and/or prevention strategies being developed for prostate cancer. Ho wever, to increase antiproliferative potency without increasing side -effec ts. the use of less calcemic analogs appears to be the most reasonable appr oach. (C) 2001 Elsevier Science Inc. All rights reserved.