Uptake of anthracycline pirarubicin via a sodium-dependent nucleoside transport system

We previously demonstrated that the cytotoxicity of anthracyclines, pirarubicin (THP) and doxorubicin (DOX), against M5076 cells was partially dominated by their intracellular amounts, which depended on the uptake efficacy of concentrative nucleoside transporter (CNT). In this study, to examine the kind of CNT involved in THP uptake by M5076 cells to which mutant CNT2 (CNT2(M)) was localized among CNT1-3, we characterized the uptake of [H-3]uridine, a representative substrate for NT, in M5076 cells and CNT2(M)-transfected cells, in comparison with the uptake of THR CNT2(M) could transport cytidine in addition to nucleoside previously reported as CNT2 substrate. CNT2(M) and cytidine-insensitive transport system contributed to Na+-dependent uptake of [H-3]uridine by M5076 cells. The [3 H]uridine uptake via cytidine-insensitive CNT in M5076 cells was increased by addition of bile acid salts. The uptake of THP by CNT2(M)-transfectant was almost the same as that by mock cells, suggesting that THP is not taken up via CNT2(M). Cytidine had no effect on the uptake of THP by M5076 cells, and the uptake was promoted by bile acid salts. Therefore, it is indicated that cytidine-insensitive CNT might be involved in THP uptake by M5076 cells.