Chidamide induces apoptosis in DLBCL cells by suppressing the HDACs/STAT3/Bcl‑2 pathway

Abstract

Diffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous malignant tumor type, and epigenetic modifications such as acetylation or deacetylation serve vital roles in its development. Chidamide, a novel histone deacetylase inhibitor, exerts an anticancer effect against various types of cancer. The present study aimed to evaluate the cellular effect of chidamide on a number of DLBCL cell lines and to investigate its underlying mechanism. The results demonstrated that chidamide induced the death of these cells in a concentration-(0-30 µmol/l) and time-dependent (24-72 h) manner, as determined using the Cell Counting Kit-8 cell viability assay. Moreover, chidamide promoted cellular apoptosis, which was identified via flow cytometry and western blot analysis, with an increase in cleaved caspase-3 expression and a decrease in Bcl-2 expression. Chidamide treatment also decreased the expression level of STAT3 and its phosphorylation, which was accompanied by the downregulation of a class-I histone deacetylase (HDAC) inhibitor, chidamide. Collectively, these data suggested that chidamide can be a potent therapeutic agent to treat DLBCL by inducing the apoptotic death of DLBCL cells by inhibiting the HDACs/STAT3/Bcl-2 pathway.

Single‐cell profiling guided combination therapy of c‐Fos and histone deacetylase inhibitors in diffuse large B‐cell lymphoma

“…LAQ824 produced anti‐proliferative, apoptosis‐related effects in DLBCL cells, associated with a reduction of the anti‐apoptotic BCL2 protein, at least in some cell lines. Similar effects were found in DLBCL cells that were incubated with chidamide, which blocks HDAC1, HDAC2, HDAC3 and HDAC10 6 (Figure 1B ), suggesting that DLBCL cells require these HDACs to survive.…”

Intratumoral talimogene laherparepvec injection with concurrent preoperative radiation in patients with locally advanced soft-tissue sarcoma of the trunk and extremities: phase IB/II trial

“…Caspase-3 expression can correlate with increased tumor cell death in a number of cancer types. [44][45][46][47] Staining for caspase-3 was increased in the post-treatment specimens. Additionally, caspase-3 staining was significantly increased in those patients that received TVEC treatment compared with those that received radiation alone.…”

Modified conditioning regimen with chidamide and high‐dose rituximab for triple‐hit lymphoma

“…It is reported that HDAC inhibitors can overcome congenital and acquired rituximab resistance in patients with B‐cell lymphoma and augment the cytotoxic activity of rituximab by upregulating the expression of CD20 in lymphoma cells. Chidamide, a new HDAC inhibitor, could be a potent therapeutic agent to treat DLBCL by inducing the DLBCL cell apoptosis by inhibiting the HDACs/STAT3/Bcl‑2 pathway 8 . Hu et al reported that chidamide combined with lenalidomide could achieved excellent outcomes in heavily pretreated aggressive DLBCL patients 9 …”

“…Chidamide, a new HDAC inhibitor, could be a potent therapeutic agent to treat DLBCL by inducing the DLBCL cell apoptosis by inhibiting the HDACs/STAT3/Bcl‑2 pathway. 8 Hu et al reported that chidamide combined with lenalidomide could achieved excellent outcomes in heavily pretreated aggressive DLBCL patients. 9 …”