Etoposide stimulates 1,25-dihydroxyvitamin D3 differentiation activity, hormone binding and hormone receptor expression in HL-60 human promyelocytic cells.
The simultaneous administration of the DNA topoisomerase II inhibitor etoposide (0.15 mM) and 1,25-dihydroxyvitamin D3 (VD3) (10 nM) synergistically induced the differentiation of HL-60 human promyelocytic leukemia cells. Similar results were obtained using U-937 human promonocytic cells, or the topoisomerase II inhibitors doxorubicin (15 nM) and mitoxantrone (2.5 nM). When sequential treatments were used, pre-incubation with VD3 had little effect on the subsequent action of etoposide, while pre-incubation with etoposide greatly potentiated the subsequent action of VD3. In addition, etoposide treatment stimulated VD3 binding activity and increased VD3 receptor mRNA and protein levels. The increase in hormone receptor expression may explain, at least in part, the capacity of topoisomerase inhibitors to potentiate the differentiation inducing activity of VD3.
Departamento de Bioquímica y Biología Molecular, Facultad de Biología, Universidad Complutense, Madrid, Spain.
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D017209:Apoptosis; D002117:Calcitriol / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D023461:Myeloid Progenitor Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009580:Nitroblue Tetrazolium / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000378:metabolism; D059005:Topoisomerase II Inhibitors
D004791:Enzyme Inhibitors; D018167:Receptors, Calcitriol; D059005:Topoisomerase II Inhibitors; D009580:Nitroblue Tetrazolium; D005047:Etoposide; D002117:Calcitriol