Sodium butyrate and panobinostat induce apoptosis of chronic myeloid leukemia cells via multiple pathways
- PMID: 30891950
- PMCID: PMC6503025
- DOI: 10.1002/mgg3.613
Sodium butyrate and panobinostat induce apoptosis of chronic myeloid leukemia cells via multiple pathways
Abstract
Purpose: Histone deacetylase inhibitor (HDACI) is a novel therapeutic option for cancer. However, the effects of HDACIs on chronic myeloid leukemia (CML) and the underlying mechanisms are still unknown. The aim of this study was to investigate the effect and the mechanism-of-action of two HDACI members, sodium butyrate (NaBu) and panobinostat (LBH589) in K562 and the adriamycin-resistant cell line K562/ADR.
Methods: Cell viability was assessed using MTT assay. Cell apoptosis was detected with flow cytometry. Cell cycle analysis and western blot were performed to explore the possible molecules related to HDACIs effects.
Results: The effect of NaBu was more powerful on K562/ADR than on K562 cells. LBH589 triggered apoptosis and inhibited the growth of K562 cells. Both HDACIs inhibited K562 and K562/ADR cells via activation of intrinsic/extrinsic apoptotic pathways and inhibition of AKT-mTOR pathway while NaBu also activated endoplasmic reticulum stress (ERS) mediated apoptotic pathway in K562/ADR cells. LBH589 reduced the expression of drug-resistant related proteins in K562 cells. However, neither NaBu nor LBH589 could significantly influence the expression of the drug-resistant related proteins in K562/ADR cells.
Conclusion: The combination of HDACI and other therapeutic strategies are likely required to overcome drug resistance in CML therapy.
Keywords: AKT-mTOR pathway; apoptosis; chronic myeloid leukemia (CML); drug resistance; histone deacetylase inhibitors (HDACIs).
© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.
Conflict of interest statement
The authors report no conflict of interest in this work.
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