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

Therapeutic effects of the novel subtype-selective histone deacetylase (HDAC) inhibitor chidamide on myeloma-associated bone disease.
Haematologica. 2018 May 17;:
Authors: He J, Chen Q, Gu H, Chen J, Zhang E, Guo X, Huang X, Yan H, He D, Yang Y, Zhao Y, Wang G, He H, Yi Q, Cai Z
Abstract
Histone deacetylases are promising therapeutic targets in hematological malignancies. In the present work, 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, including p21 and p27, among others. Furthermore, chidamide exhibited significant cytotoxicity against myeloma cells co-cultured with bone mesenchymal stromal cells and chidamide-pre-treated 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 RANKL-induced bone loss in a non-tumor-bearing mouse model. Based on our results, chidamide exerted dual anti-myeloma a...

Source: Haematologica - May 17, 2018 Category: Hematology Authors: He J, Chen Q, Gu H, Chen J, Zhang E, Guo X, Huang X, Yan H, He D, Yang Y, Zhao Y, Wang G, He H, Yi Q, Cai Z Tags: Haematologica Source Type: research