Bioreductive Activation of Antitumour Drugs, Doxorubicin and Pirarubicin, Does Not Affect Their Ability to Induce Apoptosis of Sensitive and Multidrug Resistant Leukaemia HL60 Cells

Abstract

Clinical significance of antitumour drugs is limited by multidrug resistance (MDR). We examined the effect of bioreductive activation of the anthracyclines, doxorubicin (DOX) and pirarubicin (PIRA), by cytochrome P450 reductase (CPR) on triggering apoptosis of leukaemia HL60 cells and their MDR counterparts. Cell cycle and FAS expression were investigated by flow cytometry. DNA fragmentation was examined by electrophoretic analysis and caspase-3/8 activities were determined colorimetrically. Non-activated and CPR-activated forms of DOX and PIRA (IC90) had similar efficacy in provoking G2/M arrest of sensitive HL60 as well as resistant HL60/VINC and HL60/DOX cells and in causing DNA degradation. Interestingly, HL60/VINC cells were more prone to apoptosis induced by all studied forms of these drugs. However, no change in Fas expression was observed. Bioreductive activation of DOX and PIRA does not affect their ability to induce apoptosis of sensitive and resistant HL60 leukaemia cells.