〔Abstract〕 To investigate the ferroptosis induced by sesamin in triple-negative breast cancer ( TNBC) 4T1 cells and its underlying mechanism . Methods The binding energy of sesamin with glutathione peroxidase 4 (GPX4) , solute carrier family 7 member 11 ( SLC7A11) , and P53 was analyzed by molecular docking. Mouse TNBC cell line 4T1 was used as a model . Different concentrations of sesamin were administered to 4T1 cells . The effect of sesamin on cell viability was assessed using the cell counting kit 8 (CCK-8) . Transwell assay was used to evaluate the effect of sesamin on cell migration and invasion . The contents of Fe2 + , malondialdehyde (MDA) , and reduced glutathione (GSH) in the cells were measured using kits . 2 ′,7 ′-dichlorofluorescein diacetate (DCFH-DA) probe was employed to detect the content of reactive oxygen species (ROS) in cells . Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot were performed to evaluate the expression of GPX4 , SLC7A11 , and P53 at mRNA and protein levels . Results The binding energies of sesamin with GPX4 , SLC7A11 and P53 were - 21 . 46 , - 21 . 67 , and - 27 . 03 kJ/mol , respectively . Compared with the control group , the viability of 4T1 cells in different concentrations of sesamin groups decreased gradually ( P < 0. 001) , and the migration and invasion ability of 4T1 cells in 20 , 40 , and 80 μmol/L sesamin groups decreased gradually (all P < 0. 001) . Compared with the control group , the contents of Fe2 + , MDA , and ROS in 4T1 cells of 20 , 40 , and 80 μmol/L sesamin groups increased , and the content of GSH decreased . Compared with the control group , the mRNA and protein expression of GPX4 and SLC7A11 in 4T1 cells in the sesamin treatment group decreased , and the mRNA and protein expression of P53 increased ( all P < 0. 001) . Conclusion Sesamin may induce the ferroptosis in 4T1 cells through P53/SLC7A11 /GPX4 pathway .