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Homoharringtonine promotes BCR‑ABL degradation through the p62‑mediated autophagy pathway

  • Authors:
    • Su Li
    • Zhilei Bo
    • Ying Jiang
    • Xianmin Song
    • Chun Wang
    • Yin Tong
  • View Affiliations / Copyright

    Affiliations: Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 113-120
    |
    Published online on: November 20, 2019
       https://doi.org/10.3892/or.2019.7412
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Abstract

Drug resistance to tyrosine kinase inhibitors (TKIs) is currently a clinical problem in patients with chronic myelogenous leukemia (CML). Homoharringtonine (HHT) is an approved treatment for adult patients with chronic‑ or accelerated‑phase CML who are resistant to TKIs and other therapies; however, the underlying mechanisms remain unclear. In the present study, HHT treatment demonstrated induction of apoptosis in imatinib‑resistant K562G cells by using MTS assay and western blotting, and BCR‑ABL protein was reduced. CHX chase assay revealed that HHT induced degradation of the BCR‑ABL protein, which could be reversed by autophagy lysosome inhibitors Baf‑A1 and CQ. Next, HHT treatment confirmed the induction of autophagy in K562G cells, and silencing the key autophagic proteins ATG5 and Beclin‑1 inhibited the degradation of the BCR‑ABL protein and cytotoxicity. In addition, autophagic receptor p62/SQSTM1(p62) participated during the autophagic degradation of BCR‑ABL induced by HHT, and this was confirmed by co‑immunoprecipitation, in which HHT enhanced the ubiquitination of the BCR‑ABL protein and promoted its binding to p62. In conclusion, HHT induced p62‑mediated autophagy in imatinib‑resistant CML K562G cells, thus promoting autophagic degradation of the BCR‑ABL protein and providing a novel strategy for the treatment of TKI‑resistant CML.
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Copy and paste a formatted citation
Spandidos Publications style
Li S, Bo Z, Jiang Y, Song X, Wang C and Tong Y: Homoharringtonine promotes BCR‑ABL degradation through the p62‑mediated autophagy pathway. Oncol Rep 43: 113-120, 2020.
APA
Li, S., Bo, Z., Jiang, Y., Song, X., Wang, C., & Tong, Y. (2020). Homoharringtonine promotes BCR‑ABL degradation through the p62‑mediated autophagy pathway. Oncology Reports, 43, 113-120. https://doi.org/10.3892/or.2019.7412
MLA
Li, S., Bo, Z., Jiang, Y., Song, X., Wang, C., Tong, Y."Homoharringtonine promotes BCR‑ABL degradation through the p62‑mediated autophagy pathway". Oncology Reports 43.1 (2020): 113-120.
Chicago
Li, S., Bo, Z., Jiang, Y., Song, X., Wang, C., Tong, Y."Homoharringtonine promotes BCR‑ABL degradation through the p62‑mediated autophagy pathway". Oncology Reports 43, no. 1 (2020): 113-120. https://doi.org/10.3892/or.2019.7412
Copy and paste a formatted citation
x
Spandidos Publications style
Li S, Bo Z, Jiang Y, Song X, Wang C and Tong Y: Homoharringtonine promotes BCR‑ABL degradation through the p62‑mediated autophagy pathway. Oncol Rep 43: 113-120, 2020.
APA
Li, S., Bo, Z., Jiang, Y., Song, X., Wang, C., & Tong, Y. (2020). Homoharringtonine promotes BCR‑ABL degradation through the p62‑mediated autophagy pathway. Oncology Reports, 43, 113-120. https://doi.org/10.3892/or.2019.7412
MLA
Li, S., Bo, Z., Jiang, Y., Song, X., Wang, C., Tong, Y."Homoharringtonine promotes BCR‑ABL degradation through the p62‑mediated autophagy pathway". Oncology Reports 43.1 (2020): 113-120.
Chicago
Li, S., Bo, Z., Jiang, Y., Song, X., Wang, C., Tong, Y."Homoharringtonine promotes BCR‑ABL degradation through the p62‑mediated autophagy pathway". Oncology Reports 43, no. 1 (2020): 113-120. https://doi.org/10.3892/or.2019.7412
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