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Chidamide, a histone deacetylase inhibitor, induces growth arrest and apoptosis in multiple myeloma cells in a caspase‑dependent manner

  • Authors:
    • Xiang‑Gui Yuan
    • Yu‑Rong Huang
    • Teng Yu
    • Hua‑Wei Jiang
    • Yang Xu
    • Xiao‑Ying Zhao
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    Affiliations: Department of Hematology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China
    Copyright: © Yuan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 411-419
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    Published online on: May 2, 2019
       https://doi.org/10.3892/ol.2019.10301
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Abstract

Chidamide, a novel histone deacetylase (HDAC) inhibitor, induces antitumor effects in various types of cancer. The present study aimed to evaluate the cytotoxic effect of chidamide on multiple myeloma and the underlying mechanisms involved. Viability of multiple myeloma cells upon chidamide treatment was determined by the Cell Counting Kit‑8 assay. Apoptosis induction and cell cycle alteration were detected by flow cytometry. Specific apoptosis‑associated proteins and cell cycle proteins were evaluated by western blot analysis. Chidamide suppressed cell viability in a time‑ and dose‑dependent manner. Chidamide treatment markedly suppressed the expression of type I HDACs and further induced the acetylation of histones H3 and H4. In addition, it promoted G0/G1 arrest by decreasing cyclin D1 and c‑myc expression, and increasing phosphorylated‑cellular tumor antigen p53 and cyclin‑dependent kinase inhibitor 1 (p21) expression in a dose‑dependent manner. Treatment with chidamide induced cell apoptosis by upregulating the apoptosis regulator Bax/B‑cell lymphoma 2 ratio in a caspase‑dependent manner. In addition, the combination of chidamide with bortezomib, a proteasome inhibitor widely used as a therapeutic agent for multiple myeloma, resulted in enhanced inhibition of cell viability. In conclusion, chidamide induces a marked antimyeloma effect by inducing G0/G1 arrest and apoptosis via a caspase‑dependent pathway. The present study provides evidence for the clinical application of chidamide in multiple myeloma.
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Copy and paste a formatted citation
Spandidos Publications style
Yuan XG, Huang YR, Yu T, Jiang HW, Xu Y and Zhao XY: Chidamide, a histone deacetylase inhibitor, induces growth arrest and apoptosis in multiple myeloma cells in a caspase‑dependent manner. Oncol Lett 18: 411-419, 2019.
APA
Yuan, X., Huang, Y., Yu, T., Jiang, H., Xu, Y., & Zhao, X. (2019). Chidamide, a histone deacetylase inhibitor, induces growth arrest and apoptosis in multiple myeloma cells in a caspase‑dependent manner. Oncology Letters, 18, 411-419. https://doi.org/10.3892/ol.2019.10301
MLA
Yuan, X., Huang, Y., Yu, T., Jiang, H., Xu, Y., Zhao, X."Chidamide, a histone deacetylase inhibitor, induces growth arrest and apoptosis in multiple myeloma cells in a caspase‑dependent manner". Oncology Letters 18.1 (2019): 411-419.
Chicago
Yuan, X., Huang, Y., Yu, T., Jiang, H., Xu, Y., Zhao, X."Chidamide, a histone deacetylase inhibitor, induces growth arrest and apoptosis in multiple myeloma cells in a caspase‑dependent manner". Oncology Letters 18, no. 1 (2019): 411-419. https://doi.org/10.3892/ol.2019.10301
Copy and paste a formatted citation
x
Spandidos Publications style
Yuan XG, Huang YR, Yu T, Jiang HW, Xu Y and Zhao XY: Chidamide, a histone deacetylase inhibitor, induces growth arrest and apoptosis in multiple myeloma cells in a caspase‑dependent manner. Oncol Lett 18: 411-419, 2019.
APA
Yuan, X., Huang, Y., Yu, T., Jiang, H., Xu, Y., & Zhao, X. (2019). Chidamide, a histone deacetylase inhibitor, induces growth arrest and apoptosis in multiple myeloma cells in a caspase‑dependent manner. Oncology Letters, 18, 411-419. https://doi.org/10.3892/ol.2019.10301
MLA
Yuan, X., Huang, Y., Yu, T., Jiang, H., Xu, Y., Zhao, X."Chidamide, a histone deacetylase inhibitor, induces growth arrest and apoptosis in multiple myeloma cells in a caspase‑dependent manner". Oncology Letters 18.1 (2019): 411-419.
Chicago
Yuan, X., Huang, Y., Yu, T., Jiang, H., Xu, Y., Zhao, X."Chidamide, a histone deacetylase inhibitor, induces growth arrest and apoptosis in multiple myeloma cells in a caspase‑dependent manner". Oncology Letters 18, no. 1 (2019): 411-419. https://doi.org/10.3892/ol.2019.10301
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