Growth inhibition of cancer cells by an active metabolite of a novel vitamin D prodrug.
Active vitamin D compounds have been developed that maintain antiproliferative properties with low calcemic activity. BCI-210, a novel vitamin D pro-drug developed in our laboratory, is activated through side chain hydroxylation and possesses lower calcemic activity than calcitriol. The human hepatoma cell line (HepG2) was used to produce an active metabolite, which was characterized and identified as 27-hydroxy-BCI-210. We compared the ability of 27-OH-BCI-210 with calcitriol to inhibit proliferation of prostate (LNCaP), and breast (MCF-7) cancer cells. Cells were plated in multi-well plates and incubated with vehicle or vitamin D compounds for 6 days, after which the cell numbers were determined by a colorimetric assay. 27-OH-BCI-210 produced a dose-dependent growth inhibition, although a concentration five-fold greater than calcitriol was required to produce equivalent inhibition. We also examined the antiproliferative activity of 27-OH-BCI-210 in combination with chemotherapeutic drugs. With genistein and doxorubicin, 27-OH-BCI-210 produced synergistic inhibition of proliferation of LNCaP and MCF-7 cells. These synergistic interactions suggest the potential clinical utility of 27-OH-BCI-210 in the treatment of prostate and breast tumors.
Wang
Y R
YR
Bone Care International, 1600Aspen Commons, Middleton, WI 53562, USA. ywang@bonecare.com
Wigington
D P
DP
Strugnell
S A
SA
Knutson
J C
JC
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002117:Calcitriol / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage; D004872:Ergocalciferols / Q000494:pharmacology; D005260:Female; D019833:Genistein / Q000008:administration & dosage; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism; D008297:Male; D011355:Prodrugs / Q000378:metabolism / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014807:Vitamin D / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
C506650:27-OH-BCI-210; C506649:BCI-210; D004872:Ergocalciferols; D011355:Prodrugs; D014807:Vitamin D; C042533:1 alpha-hydroxyergocalciferol; D004317:Doxorubicin; D019833:Genistein; D002117:Calcitriol