Chrysotoxine regulates ferroptosis and the PI3K/AKT/mTOR pathway to prevent cervical cancer

Initially, the effects of chrysotoxine on the cervical cancer cell line HeLa were assessed using CCK-8, transwell, colony formation, and flow cytometry to evaluate cell proliferation, invasion, migration, and apoptosis. Subsequently, network pharmacology and molecular docking techniques were employed to identify the molecular targets of chrysotoxine in cervical cancer. Finally, confocal microscopy assessed the expression levels of ROS and lipid compounds in response to chrysotoxine treatment, and the influence of chrysotoxine on signaling pathways was investigated using Western blot analysis, guided by KEGG pathway analysis.

Our cell-based experiments revealed that CTX effectively suppresses the cell proliferation, migration, invasion, and apoptosis in CC. Subsequently, we comprehensively analyzed that HSP90AA1, ESR1, PIK3CA, mTOR and MAPK1 may be the possible targets of CTX in CC by combining network pharmacology with molecular docking techniques. Finally, we observed that CTX enhances the production of intracellular ROS and excessive lipid peroxides. Simultaneously, we detected that CTX promotes ferroptosis-based p53/GPX4/SLC7A11 pathway and inhibits PI3K/AKT/mTOR pathway-induced cell death of CC by Western blot.