Dihydroartemisinin induces apoptosis in human leukemia cells HL60 via downregulation of transferrin receptor expression.

Dihydroartemisinin (DHA), a water-soluble active metabolite of artemisinin derivatives, is the safest and most effective antimalarial analog of artemisinin. In the present investigation, we assessed the apoptotic effect of DHA on leukemia HL60 cells and its regulation of transferrin receptor (TfR). Cell growth inhibition was assessed by Trypan blue exclusive staining; the expression of caspase-3, Bcl-2, and Bax in HL60 cells was evaluated by Western blotting; DHA-induced apoptosis was determined by AO/EB double staining, DNA fragmentation assay, and flow cytometric analysis; the expression of TfR in HL60 cells was examined by real-time PCR assays, Western blotting, and flow cytometric analysis. DHA could specifically reduce the mRNA and protein expression of TfR in HL60 cells, and the flow cytometric analysis presented the unity tendency that the TfR content decreased progressively in a dose-dependent manner. Consequently, DHA exhibited high anticancer activity in HL60 cells; MTT assay and growth inhibition assay showed that DHA could specifically inhibit the growth of HL60 cells in a dose-dependent (0.25-8 micromol/l) and time-dependent (12-72 h) manner. DHA-induced DNA fragmentation also induced the activation of caspase-3 and influenced the expression of Bcl-2 and Bax. Taken together, these data from our study show that DHA can induce HL60 cell apoptosis via the effect of downregulation TfR expression resulting in an induction of apoptosis through the mitochondrial pathway, and it might be a potential antileukemia strategy for leukemia therapy.