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Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
Published on: March 15, 2024
Curcumin inhibits the proliferation of diffuse large B-cell lymphoma by inducing ferroptosis via the ACSL4-SAT1-GPX4
Xiaohui Gao1, Hui Zeng2, Xiaoyan Zhao2
1Department of Pediatrics, The Affiliated Hospital of Jiaxing University, Jiaxing, China.
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 Fe2+ 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 Fe2+, 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.
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