A new anthracycline with potent anti-leukemic activity overcomes P-glycoprotein multidrug resistance |
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Authors: | W Andrivon C Monneret J Nafziger JC Florent JJ Guillosson |
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Affiliation: | Laboratoire d'Hématologie Cellulaire et Moléculaire, EA 1509, UFR des Sciences Pharmaceutiques et Biologiques, Paris, France. |
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Abstract: | In this study, we assessed the ability of a new anthracycline, moflomycin, to circumvent multidrug resistance. Moflomycin showed superior anti-proliferative activity compared to daunorubicin and doxorubicin on two resistant cell lines: leukemic HL-60 cell line resistant to daunorubicin (HL-60/DR) and breast cancerous cell line resistant to doxorubicin (MCF-7/AR). The effect of moflomycin on cell proliferation was correlated with an increased uptake and a decreased cellular efflux. The data obtained in the presence of the P-gp inhibitor, verapamil, confirmed the absence of interaction between P-gp and moflomycin. Our results indicate that moflomycin exhibits an important reduction in cross-resistance with daunorubicin and doxorubicin resulting from its ability to circumvent P-gp. |
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