Dihydroartemisinin Exerts Its Anticancer Activity through Depleting Cellular Iron via Transferrin Receptor-1 英文参考文献.docVIP
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Dihydroartemisinin Exerts Its Anticancer Activity through Depleting Cellular Iron via Transferrin Receptor-1 英文参考文献
DihydroartemisininExertsItsAnticancerActivitythrough
DepletingCellularIronviaTransferrinReceptor-1
QianBa1,NaiyuanZhou2,JuanDuan1,TaoChen1,MiaoHao1,XinyingYang1,JunyangLi1,JunYin1,
RuiaiChu1,HuiWang1*
1Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of Chinese Academy of
Sciences,ChineseAcademyofSciences,Shanghai,China,2ChinaNationalCenterforBiotechnologyDevelopment,Beijing,China
Abstract
Artemisininanditsmainactivemetabolitedihydroartemisinin,clinicallyusedantimalarialagentswithlowhosttoxicity,have
recentlyshownpotentanticanceractivitiesinavarietyofhumancancermodels.Althoughironmediatedoxidativedamage
is involved, the mechanisms underlying these activities remain unclear. In the current study, we found that
dihydroartemisinincausedcellularirondepletionintime-andconcentration-dependentmanners.Itdecreasedironuptake
anddisturbedironhomeostasisincancercells,whichwereindependentofoxidativedamage.Moreover,dihydroartemisinin
reduced the level of transferrin receptor-1 associated with cell membrane. The regulation of dihydroartemisinin to
transferrin receptor-1 could be reversed by nystatin, a cholesterol-sequestering agent but not the inhibitor of clathrin-
dependent endocytosis. Dihydroartemisinin also induced transferrin receptor-1 palmitoylation and colocalization with
caveolin-1,suggestingalipidraftsmediatedinternalizationpathwaywasinvolvedintheprocess.Also,nystatinreversedthe
influences of dihydroartemisinin on cell cycle and apoptosis related genes and the siRNA induced downregulation of
transferrin receptor-1 decreased the sensitivity to dihydroartemisinin efficiently in the cells. These results indicate that
dihydroartemisinincancounteractcancerthroughregulatingcell-surfacetransferrinreceptor-1inanon-classicalendocytic
pathway,whichmaybeanewactionmechanismofDHAindependentlyofoxidativedamage.
Citation: BaQ,Zhou N,Duan J,Chen T,HaoM, et al.(2012) Dihydroartemisinin Ex
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