Possibility of Contribution of Nucleoside Transport Systems to Pirarubicin Uptake by HL60 Cells but Not Mononuclear Cells

Previously, we reported that pirarubicin (THP), an anthracycline, was taken up, at least in part, by both human leukemic HL60 cells and mononuclear cells (MNCs) via a carrier-mediated system. In this study, the possibility of a contribution of nucleoside transport systems to the uptake of THP by 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. In HL60 cells, THP uptake was increased and decreased significantly by treatment with equilibrative nucleoside transport inhibitors, nitrobenzylthioinosine (NBMPR), nitrobenzylthioguanosine and dilazep, in the presence and absence, respectively, of an inwardly directed Na⁺-gradient. THP uptake by HL60 cells showed an overshoot in the presence of the gradient, and was decreased by treatment of the cells with monensin, indicating that the uptake partially depended on the Na⁺-gradient. In HL60 cells in which equilibrative nucleoside transport was inhibited by NBMPR, THP uptake in the presence of the gradient was inhibited by Na⁺-dependent concentrative nucleoside transport inhibitors, but no inhibition was observed in the absence of the gradient. In MNCs, conversely, there was no effect of any equilibrative nucleoside transport inhibitor or the Na⁺-gradient on THP uptake. These results suggested that THP was taken up, at least in part, via both equilibrative and concentrative nucleoside transport systems in HL60 cells, but not in MNCs.