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• W2065723669 abstract "We have studied the cytotoxicity and intracellular accumulation of two lipophilic anthracyclines, pirarubicin and idarubicin, as compared to doxorubicin, in two human tumor cell lines, MCF7 and K562, and in their doxorubicinresistant counterparts, presenting the multidrug-resistant (MDR) phenotype. The new lipophilic anthracyclines were found to present a higher cytotoxicity and accumulation than the reference anthracycline, doxorubicin, and there was a significant inverse correlation between drug accumulation and IC50 in both cell types. With the aim of identifying the reasons for the higher cytotoxicity and accumulation of lipophilic anthracyclines, we used and compared the efficiency of three MDR modulators, verapamil, quinine and S- 9788. We showed that all three were able to sensitize the resistant cells to the three anthracyclines, but with different efficiencies, S-9788 being the most active reverter and quinine the least active at equimolar doses. We also observed that there was no correlation between the abilities of a modulator to reverse resistance and to restore drug accumulation. In view of the sustained activity of the modulators to increase pirarubicin and idarubicin cytotoxicity and accumulation, as they do for doxorubicin, we conclude that the better efficiency of lipophilic anthracyclines is likely to be due to their high uptake rate rather than to a decreased activity of P-glycoprotein on these drug substrates." @default.
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• W2065723669 date "1997-07-01" @default.
• W2065723669 modified "2023-10-17" @default.
• W2065723669 title "Cellular pharmacology of lipophilic anthracyclines in human tumor cells in culture selected for resistance to doxorubicin" @default.
• W2065723669 doi "https://doi.org/10.1097/00001813-199707000-00009" @default.
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