Curcumin inhibits the proliferation of diffuse large B-cell lymphoma by inducing ferroptosis via the ACSL4-SAT1-GPX4 axis.

BACKGROUND: Curcumin exhibits anti-inflammatory, antioxidant, and anti-tumor effects. However, its specific mechanisms of action in diffuse large B-cell lymphoma (DLBCL) remain unclear. This study aims to investigate the inhibitory effect of curcumin on DLBCL cells and to elucidate the underlying molecular mechanisms, with a specific focus on its role in regulating the ferroptosis pathway. METHODS: The anti-proliferative effect of curcumin on human DLBCL cell lines (SU-DHL-2 and OCI-LY7) was assessed using the Cell Counting Kit-8 (CCK-8) assay. Transcriptome sequencing and bioinformatics analysis were performed on curcumin-treated OCI-LY7 cells to identify potential mechanisms. Ferroptosis-related indicators were evaluated, including lipid reactive oxygen species (ROS) levels (BODIPY™ C11 probe), mitochondrial membrane potential (JC-1 staining), intracellular Fe(2+) levels (FerroOrange probe), malondialdehyde (MDA) content, and glutathione (GSH/GSSG) ratio. The protein expression of key ferroptosis regulators (ACSL4, SAT1, GPX4) was analyzed by Western blot. RESULTS: Curcumin significantly inhibited the proliferation of SU-DHL-2 and OCI-LY7 cells in a concentration- and time-dependent manner. Transcriptome analysis revealed significant enrichment of differentially expressed genes in the ferroptosis pathway. Curcumin treatment led to a concentration-dependent upregulation of ACSL4 and SAT1 protein expression and downregulation of GPX4. Functionally, curcumin induced characteristic features of ferroptosis: accumulation of lipid ROS and intracellular Fe(2+), a decrease in mitochondrial membrane potential, a reduced GSH/GSSG ratio, and increased MDA levels. CONCLUSIONS: Curcumin inhibits the proliferation of DLBCL cells by activating the ferroptosis-related pathway, likely through modulating the ACSL4-SAT1-GPX4 axis. These findings provide a novel mechanistic insight into the anti-tumor activity of curcumin for DLBCL.