Caffeine Modulates Ferroptosis Through the PI3K/Akt Signaling Pathway to Inhibit Invasion and Migration of U-373 Glioblastoma Cells

Objective This study aimed to investigate the effects of caffeine on the invasion and migration of human glioblastoma U-373 cells and to elucidate its mechanism of action through the regulation of the PI3K/Akt signaling pathway and ferroptosis. Methods U-373 cells were cultured in Dulbecco's Modified Eagle's Medium (DMEM). The effects of caffeine on cell invasion, migration, apoptosis, and ferroptosis were assessed using Transwell assays, flow cytometry, cell scratch assays, and Western blotting techniques. Western blot analysis was specifically used to evaluate the expression of PI3K/Akt-related proteins and markers of ferroptosis. Results Caffeine significantly inhibited the invasion and migration of U-373 cells in a concentration-dependent manner. It also promoted apoptosis and decreased the expression of p-PI3K/PI3K and p-Akt/Akt proteins, as well as markers associated with ferroptosis. Conclusion Caffeine, through its regulation of the PI3K/Akt signaling pathway and modulation of ferroptosis, effectively suppresses the invasion and migration of U-373 glioblastoma cells. These findings suggest that caffeine could be a promising anti-glioblastoma agent and offer new insights into its potential applications in cancer treatment.