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.
Keywords:
DLBCL; chidamide; HDAC; STAT3; Bcl‑2; apoptosis.
MeSH terms
-
Aminopyridines / pharmacology*
-
Apoptosis / drug effects*
-
Benzamides / pharmacology*
-
Caspase 3 / metabolism
-
Cell Line, Tumor
-
Dose-Response Relationship, Drug
-
Gene Expression / drug effects
-
Histone Deacetylase Inhibitors / pharmacology
-
Histone Deacetylases / metabolism*
-
Humans
-
Isoenzymes / metabolism
-
Lymphoma, Large B-Cell, Diffuse / genetics
-
Lymphoma, Large B-Cell, Diffuse / metabolism
-
Lymphoma, Large B-Cell, Diffuse / pathology
-
Phosphorylation / drug effects
-
Proto-Oncogene Proteins c-bcl-2 / metabolism*
-
STAT3 Transcription Factor / genetics
-
STAT3 Transcription Factor / metabolism*
-
Signal Transduction / drug effects*
Substances
-
Aminopyridines
-
BCL2 protein, human
-
Benzamides
-
Histone Deacetylase Inhibitors
-
Isoenzymes
-
Proto-Oncogene Proteins c-bcl-2
-
STAT3 Transcription Factor
-
STAT3 protein, human
-
N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide
-
Caspase 3
-
Histone Deacetylases
Grants and funding
This work was supported by Nature Science Project of Shanxi, China (grant nos. 201701D121165 and 201901D111190), the Research Project Supported by Shanxi Scholarship Council of China (grant no. 2020–194), Key R & D Projects in Shanxi, China (grant no. 201703D421023), the Open Fund from Key Laboratory of Cellular Physiology (Shanxi Medical University), Ministry of Education, China (grant no. KLMEC/SXMU-202011) and the Shanxi ‘1331 Project’ Key Subjects Construction, China (grant no. 1331KSC).