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.
MeSH terms
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Animals
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Apoptosis / drug effects*
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Blotting, Western
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Breast Neoplasms / drug therapy
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Breast Neoplasms / metabolism
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Breast Neoplasms / pathology*
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Calcitriol / analogs & derivatives*
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Calcitriol / chemical synthesis
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Calcitriol / pharmacology
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Cell Cycle / drug effects
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Cell Proliferation / drug effects*
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Dioxoles / chemical synthesis
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Dioxoles / pharmacology*
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Female
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HT29 Cells
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Humans
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In Vitro Techniques
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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Molecular Structure
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Prostatic Neoplasms / drug therapy
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Prostatic Neoplasms / metabolism
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Prostatic Neoplasms / pathology*
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RNA, Messenger / genetics
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Real-Time Polymerase Chain Reaction
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Receptors, Calcitriol / genetics
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Receptors, Calcitriol / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Tumor Cells, Cultured
Substances
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24-cyclopropyl-9,10-secochola-5,7,10(19),22-tetraene-24-chloro-1,3-diol
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BGP-13 compound
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Dioxoles
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RNA, Messenger
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Receptors, Calcitriol
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VDR protein, human
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Calcitriol