Antitumour effects of selected plant polyphenols, gallic acid and ellagic acid, on sensitive and multidrug-resistant leukaemia HL60 cells.
Phytother Res. 2019 Mar 5. Epub 2019 Mar 5. PMID: 30838722
The aim of this study was to examine the antitumour effects of plant phenolic acids, gallic acid (GA) and ellagic acid (EA), on human promyelocytic leukaemia sensitive HL60 cell line and its resistant sublines exhibiting two MDR phenotypes: HL60/VINC (overexpressing P-glycoprotein) and HL60/MX2 (characterized by the presence of mutatedα isoform of topoisomerase II). Both studied compounds exerted comparable cytotoxic activities towards sensitive HL60 cells and their MDR counterparts. It was also found that GA and EA modulated the cellular level of reactive oxygen species in a dose-dependent and time-dependent manner. Furthermore, it was demonstrated that GA (IC) and EA (ICand IC) significantly increased the percentage of sub-G1 subpopulation of all studied leukaemia cells causing oligonucleosomal DNA fragmentation. Both compounds used at ICtriggered mainly the apoptotic death of these cells. However, GA had no effect on the activity of caspase-3 as well as caspase-8 in sensitive HL60 cells and their MDR counterparts. In contrast, EA provoked a significant activation of these caspases in all studied leukaemia cells. It was also found that lysosomes were not involved in triggering programmed death of sensitive HL60 and MDR cells by GA and EA.