title: Potent 19-norvitamin D analogs for prostate and liver cancer therapy.
abstract: The active form of vitamin D(3), 1α,25(OH)(2)D(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)(2)D(3) for prostate and liver cancer therapy. However, 1α,25(OH)(2)D(3) can cause hypercalcemia, thus, analogs of 1α,25(OH)(2)D(3) that are less calcemic but exhibit potent antiproliferative activity would be attractive as therapeutic agents. We have developed 2α-functional group substituted 19-norvitamin D(3) analogs with and without 14-epimerization. Among them, 2α- and 2β-(3-hydroxypropyl)-1α,25-dihydroxy-19-norvitamin D(3) (MART-10 and -11, respectively) and 14-epi-2α- and 14-epi-2β-(3-hydroxypropyl)-1α,25-dihydroxy-19-norvitamin D(3) (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.
authors.affiliation: Faculty of Pharmaceutical Sciences, Teikyo University, 2-11-1 Kaga, Tokyo 173-8605, Japan. akittaka@pharm.teikyo-u.ac.jp
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kittaka
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yoshida
authors.forename: Kun-Chun
authors.initials: KC
authors.lastname: Chiang
authors.forename: Masashi
authors.initials: M
authors.lastname: Takano
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sawada
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Sakaki
authors.forename: Tai C
authors.initials: TC
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008099:Liver / Q000187:drug effects; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000517:prevention & control; D008297:Male; D011467:Prostate / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000517:prevention & control
chemical_list: D000970:Antineoplastic Agents; C083610:1,25-dihydroxy-19-norvitamin D3; D002117:Calcitriol