Morin induces ferroptosis in endometrial cancer cells by down-regulating FTH1.

Ferritin heavy chain 1 (FTH1) is abnormally expressed in various cancers, but its role and mechanism in endometrial cancer (EC) remain unclear. This study aims to explore the clinical significance, biological functions and potential inhibitor of FTH1 in EC. The expression, prognosis and clinical correlation of FTH1 in EC were analyzed using TIMER, GEO, kaplan-meier plotter and UALCAN databases. Virtual screening and molecular docking were conducted for identifying potential inhibitors of FTH1. In vitro experiments were conducted using human EC cells HEC-1A and RL95-2. Cell proliferation, cell cycle and apoptosis were detected by CCK-8 assay and flow cytometry. The level of reactive oxygen species (ROS) was detected by using the DCFH-DA probe. The levels of malondialdehyde (MDA) and glutathione (GSH) were detected using the corresponding test kits. Western blot was used to detect the expression level of FTH1, AKT and p-AKT. FTH1 was highly expressed in EC tissues and was associated with a shorter overall survival time of patients. Functional enrichment analysis revealed that FTH1 was mainly involved in the iron homeostasis and ferroptosis pathways. FTH1 knockdown inhibits the proliferation of EC cells, induces cell cycle arrest at the G0/G1 phase and triggers cell apoptosis. In EC cells with FTH1 knockdown, the levels of ROS and MDA were significantly increased, accompanied by a decrease in GSH levels. Furthermore, morin had a high binding affinity with FTH1, which also inhibited the malignant phenotypes of EC cells. Morin triggered ferroptosis of EC cells by down-regulating FTH1 expression and inhibiting the PI3K/AKT pathway. FTH1 is a potential prognostic biomarker and therapeutic target for EC. Morin induces ferroptosis of EC cells by regulating FTH1-PI3K/AKT axis, providing a new candidate drug and theoretical basis for the treatment of EC.