EB 1089, a novel vitamin D analogue, has strong antiproliferative and differentiation inducing effects on cancer cells.
EB 1089 is a novel vitamin D analogue which in vitro strongly inhibits the proliferation of U937 histiocytic lymphoma cells and MCF-7 breast cancer cells, with a potency of 50 to 100 times that of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. Studies of c-myc and c-fos expression in MCF-7 cells and of differentiation markers in U937 cells show that growth inhibition by EB 1089 is accompanied by induction of differentiation. The ability of EB 1089 to affect calcium metabolism in vivo in rats is decreased, compared to 1,25(OH)2D3. This low calcemic effect combined with the strong biological effect on cancer cells in vitro, makes EB 1089 an interesting candidate for treatment of cancer.
Mathiasen
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IS
Department of Biology, LEO Pharmaceutical Products, Denmark.
Colston
K W
KW
Binderup
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D000818:Animals; D001667:Binding, Competitive; D014408:Biomarkers, Tumor; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology; D002118:Calcium / Q000652:urine; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D015394:Molecular Structure; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D018167:Receptors, Calcitriol / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology
D014408:Biomarkers, Tumor; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D014807:Vitamin D; D002117:Calcitriol; C078903:seocalcitol; D002118:Calcium