Effect of Chidamide, a Novel HDAC Inhibitor, on AML Cell Lines and Patients

Abstract

Background: Although the understanding of acute myeloid leukemia (AML) and the development of novel drugs are in rapid progress, the current outcome of AML therapy is not satisfactory. Demethylated drug decitabine (DAC) or Cytarabine has great therapeutic effect on myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). However, these two Drugs alone or combination could imporve the response rate in some AML and MDS patients. We aimed to investigate the effects of the combination of DAC and a novel histone deacetylase inhibitor-chidamide in the AML cell lines and some refractory/replaspsed AML patients' primary cell lines, including MV4-11,THP-1,Kasumi-1 and HL60 cell lines and investigage the underlying mechanisms.Methods: Cell viability was estimated by MTT assay. cell cycle were detected by PI staining. Cell apoptosis were detected by flow cytometry analysis and Annexin V /PI staining.To detect the expression of apoptosis-related proteins, including BCL-2,BCL-XL and casepase 8,western blot were performed. The target downstream of molecules were analyzed by RNA seqencing and westrn blot. The effects of the combinations were estimated using compusyn software. Results: Histone deacetylase inhibitor, chidamide is synergistic with DAC or Cytarabine,although the effect of these two combinations on these cells is not exactly the same.Histone deacetylase inhibitors in combination with Demethylated drug or Anti - pyrimidine antimetabolites both affected cell cycle and significantly induced apoptosis in AML cell lines. Conclusion: The combination of DAC or Cytarabine has synergistic effects on cell viability inhibition and enhancement effects on cell apoptosis in MV4-11,THP-1,Kasumi-1 and HL60 cell lines. These data suggest that DAC or Cytarabine used in combination with chidamide has clinical potential in the treatment of AML. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.