Behavior of N-acylated daunorubicins in MDR1 gene transfected and parental cells.
The substrate specificity of the P-glycoprotein (P-170), a multidrug transporter, was studied using N-acylated daunorubicin derivatives and four MDR1 cDNA transfected cell lines. Results showed that N-acetyl-daunorubicin is a substrate, but the longer fatty acid derivatives, N-octanoyl and N-dodecanoyl daunorubicins, are not. This conclusion was reached by flow cytometric drug uptake assay, cell proliferation assays, and confocal microscopy. It was concluded that the longer fatty acid derivatives interact with plasma membranes in a way that affected P-glycoprotein function.
Aszalos
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Division of Research and Testing, FDA, Washington, DC 20204, USA.
Pine
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Pandey
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Gottesman
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D016475:3T3 Cells; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology; D003630:Daunorubicin / Q000031:analogs & derivatives* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018432:Drug Resistance, Multiple / Q000235:genetics*; D006801:Humans; D051379:Mice; D014162:Transfection; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D016572:Cyclosporine; D003630:Daunorubicin