Therapeutic effects of the novel subtype-selective histone deacetylase inhibitor chidamide on myeloma-associated bone disease

Haematologica
Jingsong HeZhen Cai

Abstract

Histone deacetylases are promising therapeutic targets in hematological malignancies. In the work herein, we investigated the effect of chidamide, a new subtype-selective histone deacetylase inhibitor that was independently produced in China, on multiple myeloma and its associated bone diseases using different models. The cytotoxicity of chidamide toward myeloma is due to its induction of cell apoptosis and cell cycle arrest by increasing the levels of caspase family proteins p21 and p27, among others. Furthermore, chidamide exhibited significant cytotoxicity against myeloma cells co-cultured with bone mesenchymal stromal cells and chidamide-pretreated osteoclasts. Importantly, chidamide suppressed osteoclast differentiation and resorption in vitro by dephosphorylating p-ERK, p-p38, p-AKT and p-JNK and inhibiting the expression of Cathepsin K, NFATc1 and c-fos. Finally, chidamide not only prevented tumor-associated bone loss in a disseminated murine model by partially decreasing the tumor burden but also prevented rapid receptor activator of nuclear factor κ-β ligand (RANKL)-induced bone loss in a non-tumor-bearing mouse model. Based on our results, chidamide exerted dual anti-myeloma and bone-protective effects in vitro and in...Continue Reading

Citations

Nov 1, 2018·Journal of Cellular Physiology·Masoud NajafiKeywan Mortezaee
Jul 14, 2020·Phytotherapy Research : PTR·Chan-Ran ParkNam-Hun Lee
Aug 16, 2019·International Journal of Molecular Sciences·Alicia González-GonzálezCarlos Martínez-Campa
Jun 5, 2021·Advanced Drug Delivery Reviews·Leon Jia Wei TangEliza Li Shan Fong

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Methods Mentioned

BETA
acetylation
flow cytometry

Software Mentioned

GraphPad Prism

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