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首页> 外文期刊>Acta pharmacologica Sinica >Dynamic effects of autophagy on arsenic trioxide-induced death of human leukemia cell line HL60 cells
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Dynamic effects of autophagy on arsenic trioxide-induced death of human leukemia cell line HL60 cells

机译：Dynamic effects of autophagy on arsenic trioxide-induced death of human leukemia cell line HL60 cells

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Aim:To evaluate the contribution of an autophagic mechanism to the As2O3-induced death of human acute myeloid leukaemia cell line HL60 cells.Methods:The growth inhibition of HL60 cells induced by As2O3 was assessed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazohum bromide colorimetric assay.The activation of autophagy was determined with monodansylcadaverine labeling and transmission electron microscope.The role of autophagy in the As2O3-induced death of HL60 cells was assessed using autophagic and lysosomal inhibitors.Immunofluorescence,flow cytometry,and Western blot analysis were used to study the apoptotic and autophagic mechanisms.Results:After treatment with As2O3,the proliferation of HL60 cells was significantly inhibited and the formation of autophagosomes increased.The blockade of autophagy maturation with the autophagy-specific inhibitor 3-methyladenine(3-MA)or the lysosome-neutraliz-ing agent NH4Cl 1 h before As2O3 potentiated the As2O3-induced death of HL60 cells.In contrast,3-MA attenuated As2O3-induced death when administered 30 min after As2O3.3-MA and NH4Cl also inhibited As2O3-induced upregulation of microtubule-associated protein 1 light chain 3,the protein required for autophagy in mammalian cells.Following As2O3,lysosomes were activated as indicated by increased levels of cathepsins B and L.The apoptotic response of HL60 cells to As2O3 was suggested by the collapse of mitochondrial membrane potential,release of cytochrome c from mitochondria,and the activation of caspase-3.Pre-treatment with 3-MA prior to As2O3 amplified these apoptotic signals,while post-treatment with 3-MA 30 min after As2O3 attenuated the apoptotic pathways.Conclusion:Autophagy plays complex roles in the As2O3-induced death of HL60 cells;it inhibits As2O3-induced apoptosis in the initiation stage,but amplifies the As2O3-mediated apoptotic program if it is persistently activated.

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