title: Artesunate-enhanced apoptosis of human high-risk myelodysplastic cells induced by the DNA methyltransferase inhibitor decitabine.
abstract: The present study aimed to investigate whether artesunate (ART) could enhance the rate of apoptosis induced by decitabine (DAC) in the high-risk myelodysplastic syndrome (MDS) SKM-1 cell line, and examine the potential underlying mechanisms. The cytotoxicity and effect upon the apoptosis of ART and DAC in the SKM-1 cells was detected using the cell counting kit-8 assay and flow cytometry, respectively. The SKM-1 protein expression levels of activated caspase-3, -9 and -8, cleaved poly(ADP-ribose) polymerase and apoptosis-inducing factor (AIF) were measured by western blotting. The laser confocal microscope analysis revealed AIF transfer to the nucleus. The growth inhibition and apoptosis rates of the ART- and DAC-treated SKM-1 cells were significantly increased compared with those of the single agent-treated SKM-1 cells (P<0.05). In addition, ART and DAC induced caspase-dependent apoptosis, while ART, but not DAC, induced caspase-independent apoptosis via AIF transfer from the mitochondria to the nucleus. In addition, ART-DAC-induced cell death was not attenuated by the caspase-3/7 inhibitor, Ac-DEVD-CHO. The results of the present study suggested that the ART-DAC combination exhibited increased effectiveness compared with the single-agent therapy,in vitro. The ART-DAC combined therapy not only activated a caspase-dependent apoptotic pathway, but also a caspase-independent mitochondrial pathway.
authors.affiliation: Department of Hematology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Hematology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China.
authors.forename: Fuxu
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Hematology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China.
authors.forename: Shupeng
authors.initials: S
authors.lastname: Wen
authors.affiliation: Department of Hematology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Hematology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Hematology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Hematology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China ; Department of Hematology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Pan
keywords: apoptosis-inducing factor; artesunate; caspase; decitabine; myelodysplastic syndrome