PURPOSE: Ferroptosis is a new mode of regulated cell death, which is completely 
distinct from other cell death modes based on morphological, biochemical, and 
genetic criteria. This study evaluated the therapeutic role of ferroptosis in 
classic chemotherapy drugs, including the underlying mechanism.
MATERIALS AND METHODS: Cell viabilitywas detected by using the 
methylthiazoltetrazlium dye uptake method. RNAiwas used to knockout 
iron-responsive element binding protein 2, and polymerase chain reaction, 
western blot was used to evaluate the efficiency. Intracellular reduced 
glutathione level and glutathione peroxidases activitywere determined by related 
assay kit. Intracellularreactive oxygen species levelswere determined by 
flowcytometry. Electron microscopywas used to observe ultrastructure changes in 
cell.
RESULTS: Among five chemotherapeutic drugs screened in this study, cisplatin was 
found to be an inducer for both ferroptosis and apoptosis in A549 and HCT116 
cells. The depletion of reduced glutathione caused by cisplatin and the 
inactivation of glutathione peroxidase played the vital role in the underlying 
mechanism. Besides, combination therapy of cisplatin and erastin showed 
significant synergistic effect on their anti-tumor activity.
CONCLUSION: Ferroptosis had great potential to become a new approach in 
anti-tumor therapies and make up for some classic drugs, which open up a new way 
for their utility in clinic.