Epigenetic therapy with chidamide alone or combined with 5‑azacitidine exerts antitumour effects on acute myeloid leukaemia cells invitro.

Abstract

Chidamide, a selective histone deacetylase inhibitor, has antitumour effects. 5-azacitidine (5-AZA), a hypomethylating agent, is effective in treating acute myeloid leukaemia (AML) and myelodysplastic syndrome. However, to the best of our knowledge, the effect of chidamide and 5-AZA on AML cell lines has not been fully investigated. In the present study, the antileukaemia activity of chidamide, alone and in combination with 5-AZA, was assessed on different subtypes of AML cell lines (M1-M5) and primary samples from several patients with AML in vitro. The results indicated that the proliferation of leukaemia cells was significantly and dose-dependently inhibited by chidamide and 5-AZA alone or in combination. The combination also had marked synergistic effects to induce apoptosis of AML cells. The apoptosis of leukaemia cells was induced via downregulation of BCL-2 and myeloid-cell leukemia 1 (MCL-1) levels. Of note, chidamide also degraded the MCL-1 protein in venetoclax-resistant U937 cells, in which the MCL-1 protein is upregulated. In addition, chidamide was able to induce myeloid differentiation (with CD11b upregulation) of AML cell lines or monocytic/dendritic differentiation (with CD86 upregulation) of primary cultured cells from several patients with AML. Chidamide was also able to promote the differentiation of the venetoclax-resistant U937 cell line by upregulating CD11b expression. In conclusion, chidamide alone or combined with 5-AZA may be an effective therapy for AML.