Tamarixetin induces ferroptotic stress through the SLC7A11–GPX4 axis and triggers a compensatory NRF2 response

Here, we investigated whether Tamarixetin induces ferroptotic stress in hepatoma cells and how nuclear factor erythroid 2-related factor 2 (NRF2) signaling responds to this process. Tamarixetin selectively reduced hepatoma cell viability, increased lipid peroxidation, and these effects were partially rescued by ferrostatin-1.

Transcriptome analysis revealed enrichment of ferroptosis- and glutathione metabolism-related pathways, highlighting redox-associated genes centered on the SLC7A11–glutathione peroxidase 4 (GPX4) axis. Tamarixetin also increased NRF2 target gene expression, indicating activation of a compensatory antioxidant response to oxidative stress. Molecular docking further suggested a potential interaction between Tamarixetin and the xCT transporter.