Contribution of the Nucleoside Transport System to Doxorubicin Transport in HL60 Cells but Not in Mononuclear Cells

Previously, we reported that pirarubicin (THP), an anthracycline, was transported, at least in part, via a nucleoside transport system in human leukemic HL60 cells, but not in mononuclear cells (MNCs). In this study, the contribution of the nucleoside transport system to the transport of other anthracyclines, doxorubicin (DOX), daunorubicin (DNR) and idarubicin (IDA), in HL60 cells and MNCs was investigated. The experiments were performed after both types of cells had been pretreated with a metabolic inhibitor, 2,4-dinitrophenol, to deplete cellular ATP. The DOX uptake by HL60 cells was partially inhibited by inhibitors of equilibrative nucleoside transporters. In HL60 cells, moreover, the uptake of DOX depended on an inwardly directed Na⁺-gradient, and was inhibited by concentrative nucleoside transporters, but there was no change in the DNR or IDA uptake under any of these conditions. On the other hand, the uptake of the three drugs by MNCs was not affected by any inhibitors of the nucleoside transporters, and there was no dependence of the uptake on an Na⁺-gradient. These results suggested that DOX, but not DNR or IDA, was partially transported in HL60 cells via the nucleoside transport system, whereas in MNCs the system did not contribute to the uptake of any of these three drugs. Thus, nucleoside transport systems contributing to the transport of anthracyclines may be different among different derivatives and cell types.