Quercetin Triggers Induction of Apoptotic and Lysosomal Death of Sensitive and Multidrug Resistant Leukaemia HL60 Cells

Multidrug resistance (MDR) constitutes the major cause of the failure in anticancer therapy. One of the most important mechanisms leading to the occurrence of MDR is related to the modulation of cellular death pathways. The aim of this study was to determine the effect of quercetin (Q) on triggering the programed death of human promyelocytic leukemia sensitive cells HL60 as well as multidrug resistant HL60/VINC cells overexpressing P-glycoprotein and HL60/MX2 cells characterized by the presence of mutated α isoform of topoisomerase II and the absence of β isoform of this enzyme. Q exerted comparable cytotoxic activities toward sensitive HL60 cells and their MDR counterparts. It was also found that this compound modulated the cellular level of reactive oxygen species (ROS) and led to the marked decrease in cellular GSH level. Furthermore, it was demonstrated that Q used at IC50 and IC90 significantly increased the percentage of sub-G1 subpopulation of all studied leukemia cells causing oligonucleosomal DNA fragmentation. The present study also indicated that Q used at IC90 triggers predominantly programed cell death of sensitive HL60 cells and their MDR counterparts by induction of apoptosis occurring with the involvement of caspase-3 and caspase-8 as well as by lysosome membrane permeabilization-dependent mechanisms.