Artesunate-enhanced apoptosis of human high-risk myelodysplastic cells induced by the DNA methyltransferase inhibitor decitabine

Wang,Ying; Wang,Fuxu; Wen,Shupeng; Guo,Yujie; Liu,Xuan; Zhang,Xuejun; Pan,Ling

doi:10.3892/ol.2015.3121

Artesunate-enhanced apoptosis of human high-risk myelodysplastic cells induced by the DNA methyltransferase inhibitor decitabine

Authors:
- Ying Wang
- Fuxu Wang
- Shupeng Wen
- Yujie Guo
- Xuan Liu
- Xuejun Zhang
- Ling Pan
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Affiliations: Department of Hematology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China
Published online on: April 16, 2015 https://doi.org/10.3892/ol.2015.3121
Pages: 2449-2454
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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