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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.

Abstract
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.
AuthorsLiron Berkovich, Amnon C Sintov, Shimon Ben-Shabat
JournalInvestigational new drugs (Invest New Drugs) Vol. 31 Issue 2 Pg. 247-55 (Apr 2013) ISSN: 1573-0646 [Electronic] United States
PMID22661288 (Publication Type: Journal Article)
Chemical References
  • 24-cyclopropyl-9,10-secochola-5,7,10(19),22-tetraene-24-chloro-1,3-diol
  • BGP-13 compound
  • Dioxoles
  • RNA, Messenger
  • Receptors, Calcitriol
  • VDR protein, human
  • Calcitriol
Topics
  • Animals
  • Apoptosis (drug effects)
  • Blotting, Western
  • Breast Neoplasms (drug therapy, metabolism, pathology)
  • Calcitriol (analogs & derivatives, chemical synthesis, pharmacology)
  • Cell Cycle (drug effects)
  • Cell Proliferation (drug effects)
  • Dioxoles (chemical synthesis, pharmacology)
  • Female
  • HT29 Cells
  • Humans
  • In Vitro Techniques
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Molecular Structure
  • Prostatic Neoplasms (drug therapy, metabolism, pathology)
  • RNA, Messenger (genetics)
  • Real-Time Polymerase Chain Reaction
  • Receptors, Calcitriol (genetics, metabolism)
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured

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