RT Journal Article SR Electronic T1 Evaluation of 19-Nor-2α-(3-hydroxypropyl)-1α,25-dihydroxyvitamin D3 as a Therapeutic Agent for Androgen-dependent Prostate Cancer JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 3547 OP 3553 VO 29 IS 9 A1 JOHN N. FLANAGAN A1 SHASHA ZHENG A1 KUN-CHUN CHIANG A1 ATSUSHI KITTAKA A1 TOSHIYUKI SAKAKI A1 SACHIE NAKABAYASHI A1 XIANSI ZHAO A1 REMCO A. SPANJAARD A1 KELLY S. PERSONS A1 JEFFREY S. MATHIEU A1 MICHAEL F. HOLICK A1 TAI C. CHEN YR 2009 UL http://ar.iiarjournals.org/content/29/9/3547.abstract AB The high incidence of prostate cancer and lack of an effective, long-term treatment for metastatic disease highlights the need for more potent non-calcemic vitamin D analogs as potential alternative or combinational prostate cancer therapies. Among the analogs, 19-nor-1α,25-dihydroxyvitamin D2 (19-nor-1α,25(OH)2D2) known as paricalcitol or Zempler, has less calcemic effects and an equipotential activity as 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) in several in vivo and in vitro systems. It was recently demonstrated that a modified analog of paricalcitol, 19-nor-2α-(3-hydroxypropyl)-1α,25-dihydroxyvitamin D3 (MART-10) compared to 1α,25(OH)2D3 was more effective in inhibiting proliferation of an immortalized normal prostate cell line (PZ-HPV-7) (1,000-fold) and invasion of PC-3 prostate cancer cells (10-fold). In this study, the effects of MART-10 and 1α,25(OH)2D3 on proliferation, vitamin D receptor transactivation, vitamin D-binding protein (DBP) binding, CYP24A1 (24-OHase) substrate hydroxylation kinetics, and induction of CYP24A1 gene expression were compared in an androgen-dependent prostate cancer cell model, LNCaP. The results demonstrated that MART-10 was 1,000-fold more active than 1α,25(OH)2D3 in inhibiting LNCaP cell proliferation. MART-10 was more active than 1α,25(OH)2D3 in up-regulating a vitamin D receptor-responsive Luciferase construct and inducing CYP24A1 gene expression in LNCaP prostate cancer cells. In addition, MART-10 has a lower affinity for DBP and less substrate degradation by CYP24A1 compared to 1α,25(OH)2D3, indicating that MART-10 has more bioavailability and a longer half-life. Thus, these data suggest that MART-10 may be a potential candidate as a therapeutic agent for prostate cancer, especially for patients who fail in conventional therapies.