A NEW ANTHRACYCLINE WITH POTENT ANTILEUKEMIC ACTIVITY OVERCOMES P-GLYCOPROTEIN MULTIDRUG-RESISTANCE

In this study, we assessed the ability of a new anthracycline, moflomy cin, to circumvent multidrug resistance. Moflomycin showed superior an ti-proliferative activity compared to daunorubicin and doxorubicin on two resistant cell lines: leukemic HL-60 cell line resistant to daunor ubicin (HL-60/DR) and breast cancerous cell line resistant to doxorubi cin (MCF-7/AR). The effect of moflomycin on cell proliferation was cor related with an increased uptake and a decreased cellular efflux. The data obtained in the presence of the P-gp inhibitor, verapamil, confir med the absence of interaction between P-gp and moflomycin. Our result s indicate that moflomycin exhibits an important reduction in cross-re sistance with daunorubicin and doxorubicin resulting from its ability to circumvent P-gp. (C) 1998 Elsevier Science Ltd. All rights reserved .