Open AccessSodium butyrate and panobinostat induce apoptosis of chronic myeloid leukemia cells via multiple pathways
Author(s) -
Jia Xiaoyuan,
Zheng Yinsuo,
Guo Yanzi,
Chen Kan
Publication year - 2019
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.613
Subject(s) - sodium butyrate , panobinostat , k562 cells , myeloid leukemia , apoptosis , cancer research , pi3k/akt/mtor pathway , protein kinase b , viability assay , pharmacology , biology , histone deacetylase , microbiology and biotechnology , chemistry , cell culture , biochemistry , histone , genetics , gene
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.