Transport mechanisms of idarubicin, an anthracycline derivative, in human leukemia HL60 cells and mononuclear cells, and comparison with those of its analogs.
Transport mechanisms of idarubicin (IDA) in HL60 cells, as leukemia cells, and human mononuclear cells (MNCs), as normal cells, were investigated, and compared with those of its analogs. The uptake of IDA by both cell types was temperature- and concentration-dependent, was inhibited competitively by daunorubicin (DNR) and noncompetitively by adriamycin (ADR), and was stimulated by preloading of the cells with DNR and ADR, indicating the partial involvement of a carrier-mediated mechanism. On pretreatment of the cells with 2,4-dinitrophenol, IDA uptake by HL60 cells increased, but that by MNCs decreased, suggesting that IDA was partially taken up into HL60 cells via an energy-independent carrier system, and into MNCs via an energy-dependent one. We speculated that in HL60 cells the carrier concerned with IDA uptake was common to DNR and ADR, and that the binding site of IDA on the carrier was the same as that for DNR, but not that for ADR, while in MNCs the carrier system consisted of, at least in part, a carrier for DNR uptake and one for ADR uptake, and the binding site of IDA was identical to that for DNR in the former, but different from that for ADR in the latter. It appeared that the uptake of IDA was greater than those of pirarubicin, DNR and ADR in both HL60 cells and MNCs, and that IDA was incorporated into MNCs more efficiently than into HL60 cells because of the higher uptake efficacy of the carrier(s).
Nagasawa
K
K
Department of Hospital Pharmacy, Faculty of Pharmaceutical Sciences, Kyoto Pharmaceutical University.
Ohnishi
N
N
Yokoyama
T
T
D019297:2,4-Dinitrophenol / Q000494:pharmacology; D000903:Antibiotics, Antineoplastic / Q000378:metabolism* / Q000493:pharmacokinetics; D000963:Antimetabolites / Q000494:pharmacology; D001665:Binding Sites; D001692:Biological Transport; D001693:Biological Transport, Active; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D003630:Daunorubicin / Q000378:metabolism; D004058:Diffusion; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000031:analogs & derivatives / Q000378:metabolism; D018922:HL-60 Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D015255:Idarubicin / Q000378:metabolism* / Q000493:pharmacokinetics; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D013696:Temperature
D000903:Antibiotics, Antineoplastic; D000963:Antimetabolites; D002352:Carrier Proteins; D004317:Doxorubicin; C027260:pirarubicin; D019297:2,4-Dinitrophenol; D015255:Idarubicin; D003630:Daunorubicin