Abstract
The effectiveness of N-[2-(dimethylamino) ethyl]acridine-4-carboxamide (DACA) relative to that of amsacrine, idarubicin, daunorubicin and paclitaxel against three different forms of multidrug resistance (MDR) was determined using two sublines of the CCRF-CEM human leukaemia cell line, the P-glycoprotein-expressing CEM/VLB100 subline and the MRP-expressing CEM/E1000 subline, and two extended-MDR sublines of the HL60 human leukaemia cell line, HL60/E8 and HL60/V8. DACA was effective against P-glycoprotein-mediated MDR and MRP- mediated MDR, whereas the extended-MDR pheno- type showed only low levels of resistance (<2-fold) to DACA. In comparison, idarubicin was ineffec- tive against the MRP and extended-MDR phenotypes. Repeated exposure of the K562 human leukaemia cell line to DACA (55, 546 or 1092 nM for 3 days over 10 weeks) did not result in the development of any significant drug resistance. We conclude that DACA has the potential to treat refractory leukaemia.
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Received: 5 May 1996/Accepted: 16 August 1996
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Davey, R., Su, G., Hargrave, R. et al. The potential of N-[2-(dimethylamino)ethyl]acridine-4-carboxamide]to circumvent three multidrug-resistance phenotypes in vitro. Cancer Chemother Pharmacol 39, 424–430 (1997). https://doi.org/10.1007/s002800050593
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DOI: https://doi.org/10.1007/s002800050593