THE POTENTIAL OF N-[2-(DIMETHYLAMINO)ETHYL]ACRIDINE-4-CARBOXAMIDE TO CIRCUMVENT 3 MULTIDRUG-RESISTANCE PHENOTYPES IN-VITRO

The effectiveness of N-[2-(dimethylamino) ethyl]acridine-4-carboxamide (DACA) relative to that of amsacrine, idarubicin, daunorubicin and pa clitaxel against three different forms of multidrug resistance (MDR) w as determined using two sublines of the CCRF-CEM human leukaemia cell line, the P-glycoprotein-expressing CEM/VLB100 subline and the MRP-exp ressing CEM/E1000 subline, and two extended-MDR sublines of the HL60 h uman leukaemia cell line, HL60/E8 and HL60/V8. DACA was effective agai nst P-glycoprotein-mediated MDR and MRP-mediated MDR, whereas the exte nded-MDR phenotype showed only low levels of resistance (< 2-fold) to DACA. In comparison, idarubicin was ineffective against the MRP and ex tended-MDR phenotypes. Repeated exposure of the K562 human leukaemia c ell 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 conc lude that DACA has the potential to treat refractory leukaemia.