title: Chidamide, a novel histone deacetylase inhibitor, inhibits the viability of MDS and AML cells by suppressing JAK2/STAT3 signaling.
abstract: Many studies have indicated that histone deacetylase (HDAC) activity is always increased in a lot of human tumors, and inhibition of HDAC activity is a promising new strategy in the treatment of cancers. Chidamide, a novel HDAC inhibitor of the benzamide class, is currently under clinical trials. In this study, we aimed to investigate the antitumor activity of Chidamide on myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) cell lines and explore the possible mechanism. Chidamide exhibited efficient anti-proliferative activity on MDS and AML cells in a time- and dose-dependent manner, accompanied by cell cycle arrest at G0/G1 phase and cell apoptosis. Importantly, Chidamide possessed potent HDAC inhibition property, as evaluated by HDAC activity analysis and acetylation of histone H3 and H4. Moreover, Chidamide significantly increased the expression of Suppressors of cytokine signaling 3 (SOCS3), reduced the expression of Janus activated kinases 2 (JAK2) and Signal transducer and activator of transcription 3 (STAT3), and inhibited STAT3 downstream genes, including c-Myc, Bcl-xL, and Mcl-1, which are involved in cell cycle progression and anti-apoptosis. Therefore, we demonstrate that Chidamide exhibits potent inhibitory effect on cell viability of MDS and AML cells, and the possible mechanism may lie in the downregulation of JAK2/STAT3 signaling through SOCS3 upregulation. Our data provide rationale for clinical investigations of Chidamide in MDS and AML.
authors: Department of Hematology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai, China.
authors: Sida
authors: S
authors: Zhao
authors: Department of Hematology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai, China.
authors: Juan
authors: J
authors: Guo
authors: Department of Hematology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai, China.
authors: Youshan
authors: Y
authors: Zhao
authors: Department of Hematology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai, China.
authors: Chengming
authors: C
authors: Fei
authors: Department of Hematology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai, China.
authors: Qingqing
authors: Q
authors: Zheng
authors: Department of Hematology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai, China.
authors: Xiao
authors: X
authors: Li
authors: Department of Hematology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai, China.
authors: Chunkang
authors: C
authors: Chang
keywords: Chidamide; STAT3; acute myeloid leukemia; histone deacetylase inhibitor; myelodysplastic syndromes