Artesunate Enhanced Apoptosis of Human High Risk MDS Cells Induced By the DNMT Inhibitor Decitabine

Abstract: The present study evaluated whether the artesunate (ART) could enhance the apoptosis induced by decitabine (DAC) in SKM-1 cells, and to explore its potential mechanisms. Cytotoxicity of the combination of ART and DAC on SKM-1 cells was detected by CCK-8 assay and the apoptosis rate of high-risk myelodysplastic syndrome (MDS) cell line, SKM-1 cells was measured by flow cytometry. Protein expression levels of activated caspase-3, caspase-9, caspase-8, cleaved PARP and AIF in SKM-1 cells were measured by Western blot. Laser confocal microscope analysis showed AIF transfer to the nucleus. The growth inhibition rate and the apoptosis rate of SKM-1cells treated with the combination of ART and DAC was significantly increased compared with that of SKM-1 cells treated with the single agent (P<0.05). Both ART and DAC could induce caspase-dependent apoptosis, while ART, but not DAC, also induced caspase-independent apoptosis via AIF transfer from mitochondria to the nucleus. Additionally, the combination of the two agents induced cell death was not attenuated by caspase3,7 inhibitor Ac-DEVD-CHO. Our result suggested that the ART–DAC combination was more effective than single-agent therapy in vitro. Both compounds not only activated caspase-dependent pathway but also activated a caspase-independent mitochondrial pathway.