Effects of artemisinin derivative SM1044 on acute myeloid leukemia cell line HL60

Objective To investigate the proliferation inhibition and apoptosis-inducing effects and its potential mechanisms of artemisinin derivative SM1044 on HL60 cells(acute myeloid leukemia cell line).Methods Cell counting kit8(CCK-8)assay was performed to detect the proliferation inhibition induced by SM1044 on HL60 cells.Cell apoptosis and mitochondria membrane potential were assessed with flow cytometry.Expressions of apoptosis related proteins caspase-3,caspase-8,caspase-9 and poly ADP-ribose polymerase(PARP) were determined by Western blot.Results SM1044 displayed significant anti-proliferative effect on HL60 cells,with 50% inhibiting concentration(IC50) value of 0.053 μmol/L,and its anti-proliferative effect was better than other artemisinin derivatives.Furthermore,it induced apoptosis and reduced mitochondria membrane potential of HL60 cells in a dose-dependent manner.As the HL60 cells were treated with the different concentrations of SM1044(0,0.05,0.1 and 1 μ mol/L) for 24 h,the cell apoptosis rates were 3.15%,16.75%,32.53% and 49.33% respectively(r=0.947,P0.05),and the rates of mitochondrial transmembrane potential loss were 10.3%,26.1%,32.7% and 51.25 respectively(r=0.963,P0.05).In addition,SM1044 could induce the activation of caspase-8 and caspase-9,then activated caspase-3 and finally cleaved PARP.Conclusions SM1044 efficiently inhibited proliferation and induced apoptosis of HL60 cells,which could be caused by both the extrinsic and intrinsic apoptotic pathways.