Chidamide, a novel histone deacetylase inhibitor, inhibits multiple myeloma cells proliferation through succinate dehydrogenase subunit A.

Most patients with multiple myeloma (MM) would finally relapse despite the fact that initial MM may turn to remission by conventional chemotherapy. Current chemotherapy regimens have limited effect on relapse MM patients. As a new histone deacetylase inhibitor, chidamide has been used in malignancy treatment. However, it is still unknown if chidamide can be used in MM. Here, by RNA sequencing, succinate dehydrogenase subunit A (SDHA) was screened to be the key molecule modulated by chidamide. SDHA was downregulated in MM patients and the expression of SDHA had negative correlation with the severity of MM. In vitro, chidamide inhibited proliferation and invasion of MM cells, and this effect vanished after knocking down SDHA. Lenalidomide and low dose of bortezomib had synergistic effect with chidamide, and similarly this effect was attenuated by SDHA siRNA. Moreover, chidamide decreased the production of reaction oxygen species (ROS) via SDHA. In a word, by targeting the key molecule SDHA, chidamide may represent a promising strategy in MM treatment.