Inhibition of cancer growth and induction of apoptosis by BGP-13 and BGP-15, new calcipotriene-derived vitamin D3 analogs, in-vitro and in-vivo studies.
One of the most innovative approaches to the treatment of cancer entails the use of 1α,25-dihydroxyvitamin D3 (calcitriol) analogs to inhibit cancer cell growth. We demonstrate here that BGP-13, a new calcipotriene-based 1α,25-dihydroxyvitamin D3 analog that we synthesized in our laboratory, inhibits the growth of prostate cancer (LNCaP), breast cancer (MCF-7), and colon cancer (HT-29) cell lines. Moreover, we also show that BGP-13 causes cells both to accumulate in G0-G1 and to activate caspase-3 and undergo apoptosis. In addition, we observed elevated vitamin D receptor (VDR) mRNA and protein levels in both LNCaP and MCF-7 cells following the exposure of the two cell lines to BGP-13. Importantly, we found that both the new analog BGP-13 and also BGP-15, another calcipotriene-based analog we synthesized previously and about which we published recently, inhibit the growth of HT-29 tumor xenografts in nude mice.
Department of Biomedical Engineering, Faculty of Engineering Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Liron
L
Berkovich
Amnon C
AC
Sintov
Shimon
S
Ben-Shabat
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D004149:Dioxoles / Q000138:chemical synthesis / Q000494:pharmacology*; D005260:Female; D019073:HT29 Cells; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D015394:Molecular Structure; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
C550909:24-cyclopropyl-9,10-secochola-5,7,10(19),22-tetraene-24-chloro-1,3-diol; C583566:BGP-13 compound; D004149:Dioxoles; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; C579457:VDR protein, human; D002117:Calcitriol