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Effects of potent vitamin D 3 analogs on clonal proliferation of human prostate cancer cell lines
Author(s) -
de Vos Sven,
Holden Stuart,
Heber David,
Elstner Elena,
Binderup Lise,
Uskokovic Milan,
Rude Bob,
Chen Dan Lin,
Le Jennifer,
Cho Steve K.,
Koeffler H. Phillip
Publication year - 1997
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/(sici)1097-0045(19970501)31:2<77::aid-pros1>3.0.co;2-e
Subject(s) - lncap , clonogenic assay , prostate cancer , prostate , cell growth , stereochemistry , growth inhibition , vitamin d and neurology , cell culture , endocrinology , vitamin , medicine , cancer research , biological activity , cancer , cell , biology , biochemistry , chemistry , in vitro , genetics
BACKGROUND Management of prostate cancer that has spread outside of the prostate capsule is a difficult problem. Innovative, non‐toxic approaches to the disease are required. New, relatively non‐toxic vitamin D 3 analogs have recently been synthesized. We report that several of these compounds have marked antiproliferative effects on prostate cells. METHODS The clonal antiproliferative activity of five novel analogs of 1,25 dihydroxyvitamin D 3 [1,25(OH) 2 D 3 , (cmpd C)] as well as 1,25(OH) 2 D 3 itself was tested on three human prostate cancer cell lines (PC‐3, LNCaP, and DU‐145). The analogs were 20‐epi‐22oxa‐24a,26a,27a‐tri‐homo‐1α,25(OH) 2 D 3 (code name: KH 1060); 24a26a27a‐tri‐homo‐22,24‐dienelα,25(OH) 2 D 3 (code name: EB 1089); 1,25(OH) 2 ‐16ene‐D 3 (code name: HM); 1,25(OH) 2 ‐16ene‐23yne‐D 3 (code name: V); 1,25(OH) 2 ‐20‐epi‐D 3 (code name: MC 1288)]. RESULTS With the parent compound [1,25(OH) 2 D 3 ], the effective dose that inhibited 50% clonogenic growth of PC‐3 and LNCaP was 10 −8 M and 7 x 10 −9 M, respectively. For these prostate cancer cell lines, KH 1060 was the most potent analog by an order of 25‐ to 35‐fold as compared to cmpd C. The second and third most potent analogs were HM and MC 1288. DU‐145 was resistant to all the vitamin D 3 analogs. The major side‐effect of 1,25(OH) 2 D 3 is the production of hypercalcemia. The relative inhibitory index (RII) was determined by comparing the antiproliferative activity of the analog to its ability to produce hypercalcemia in mice injected intraperitoneally every other day. The KH 1060 had the best RTI: 50‐ to 70‐fold greater than 1,25(OH) 2 D 3 for PC‐3 and LNCaP, respectively. CONCLUSIONS A trial of one or more of these innovative compounds should be considered for treatment of minimal residual disease of prostate cancer. Prostate 31:77–83, 1997. © 1997 Wiley‐Liss, Inc.