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Article

Proteasome inhibitor mg‑132 enhances histone deacetylase inhibitor saha‑induced cell death of chronic myeloid leukemia cells by an ros‑mediated mechanism and downregulation of the bcr‑abl fusion protein

  • Authors:
    • Wenjing Zhou
    • Weiwei Zhu
    • Liya Ma
    • Feng Xiao
    • Wenbin Qian
  • View Affiliations / Copyright

    Affiliations: Institute of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
  • Pages: 2899-2904
    |
    Published online on: September 2, 2015
       https://doi.org/10.3892/ol.2015.3665
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Abstract

Recently, there has been progress in the treatment of chronic myeloid leukemia (CML). However, novel therapeutic strategies are required in order to address the emerging problem of imatinib resistance. Histone deacetylase inhibitors (HDACi) and proteasome inhibitors are promising alternatives, and may be amenable to integration with current therapeutic approaches. However, the mechanisms underlying the interaction between these two agents remain unclear. The present study assessed the cytotoxic effect of the HDACi, suberoylanilide hydroxamic acid (SAHA), in combination with the proteasome inhibitor, MG‑132, in imatinib‑sensitive K562 and imatinib‑resistant K562G cells, and investigated the mechanism underlying this effect. Cell viability was measured using the 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide method and protein expression levels were determined by western blotting. Reactive oxygen species (ROS) generation levels were observed under a fluorescence microscope The results indicated that SAHA and MG‑132 act in a synergistic manner to induce cell death in K562 and K562G cells. This effect was associated with Bcr‑Abl downregulation and the production of ROS. Notably, the ROS scavenger, N‑acetyl‑L‑cysteine, almost fully reversed the cell death and Bcr‑Abl downregulation that was induced by the combination of SAHA and MG‑132. By contrast, the pan‑caspase inhibitor, z‑VAD‑fmk, only partially reversed the cell death induced by these two drugs in CML cells. These results indicated that increased intracellular ROS levels are important in the induction of cell death and the downregulation of Bcr‑Abl. In conclusion, the present results suggested that combined SAHA and MG‑132 may be a promising treatment for CML.
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Copy and paste a formatted citation
Spandidos Publications style
Zhou W, Zhu W, Ma L, Xiao F and Qian W: Proteasome inhibitor mg‑132 enhances histone deacetylase inhibitor saha‑induced cell death of chronic myeloid leukemia cells by an ros‑mediated mechanism and downregulation of the bcr‑abl fusion protein. Oncol Lett 10: 2899-2904, 2015.
APA
Zhou, W., Zhu, W., Ma, L., Xiao, F., & Qian, W. (2015). Proteasome inhibitor mg‑132 enhances histone deacetylase inhibitor saha‑induced cell death of chronic myeloid leukemia cells by an ros‑mediated mechanism and downregulation of the bcr‑abl fusion protein. Oncology Letters, 10, 2899-2904. https://doi.org/10.3892/ol.2015.3665
MLA
Zhou, W., Zhu, W., Ma, L., Xiao, F., Qian, W."Proteasome inhibitor mg‑132 enhances histone deacetylase inhibitor saha‑induced cell death of chronic myeloid leukemia cells by an ros‑mediated mechanism and downregulation of the bcr‑abl fusion protein". Oncology Letters 10.5 (2015): 2899-2904.
Chicago
Zhou, W., Zhu, W., Ma, L., Xiao, F., Qian, W."Proteasome inhibitor mg‑132 enhances histone deacetylase inhibitor saha‑induced cell death of chronic myeloid leukemia cells by an ros‑mediated mechanism and downregulation of the bcr‑abl fusion protein". Oncology Letters 10, no. 5 (2015): 2899-2904. https://doi.org/10.3892/ol.2015.3665
Copy and paste a formatted citation
x
Spandidos Publications style
Zhou W, Zhu W, Ma L, Xiao F and Qian W: Proteasome inhibitor mg‑132 enhances histone deacetylase inhibitor saha‑induced cell death of chronic myeloid leukemia cells by an ros‑mediated mechanism and downregulation of the bcr‑abl fusion protein. Oncol Lett 10: 2899-2904, 2015.
APA
Zhou, W., Zhu, W., Ma, L., Xiao, F., & Qian, W. (2015). Proteasome inhibitor mg‑132 enhances histone deacetylase inhibitor saha‑induced cell death of chronic myeloid leukemia cells by an ros‑mediated mechanism and downregulation of the bcr‑abl fusion protein. Oncology Letters, 10, 2899-2904. https://doi.org/10.3892/ol.2015.3665
MLA
Zhou, W., Zhu, W., Ma, L., Xiao, F., Qian, W."Proteasome inhibitor mg‑132 enhances histone deacetylase inhibitor saha‑induced cell death of chronic myeloid leukemia cells by an ros‑mediated mechanism and downregulation of the bcr‑abl fusion protein". Oncology Letters 10.5 (2015): 2899-2904.
Chicago
Zhou, W., Zhu, W., Ma, L., Xiao, F., Qian, W."Proteasome inhibitor mg‑132 enhances histone deacetylase inhibitor saha‑induced cell death of chronic myeloid leukemia cells by an ros‑mediated mechanism and downregulation of the bcr‑abl fusion protein". Oncology Letters 10, no. 5 (2015): 2899-2904. https://doi.org/10.3892/ol.2015.3665
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