In vitro study demonstrates that Nei-Xiao-Luo-Li-San suppresses Toledo diffuse large B-cell lymphoma progression, indicating ATF5 and HDAC modulation as key therapeutic mechanisms.
Key Points
To evaluate the biological actions of Nei-Xiao-Luo-Li-San (NXLLS) on Toledo diffuse large B-cell lymphoma cells and characterize the molecular and epigenetic mechanisms driving its effects.
Characterized NXLLS chemically using liquid chromatography–mass spectrometry (LC–MS) and high-performance liquid chromatography (HPLC) to identify representative compounds.
Assessed cell viability, migration, invasion, and cell-cycle distribution in Toledo DLBCL cells exposed to NXLLS.
Profiled transcriptional and epigenetic responses using RNA sequencing, network pharmacology, ELISA, and lentiviral ATF5 overexpression and knockdown assays.
NXLLS decreased cell viability, migration, and invasion in Toledo DLBCL cells, while inducing G1-phase cell-cycle accumulation and lowering VEGF levels.
Transcriptomic profiling revealed downregulation of histone deacetylase (HDAC) pathways, accompanied by decreased HDAC expression and increased Ac-H3K9 and Ac-H3K27 levels.
Knockdown of ATF5 recapitulated the cellular and epigenetic alterations caused by NXLLS, identifying ATF5 as a candidate downstream mediator of the herbal formulation.