Figure 6.

A schematic illustration of evodiamine (EVO)-induced ferroptosis through suppression of GPX4 in human bladder cancer cells. In TCCSUP human bladder cancer cells, EVO induces cell death and G2/M cell cycle arrest and inhibits cell migration and EMT. Furthermore, EVO suppresses the expression of GPX4, an antioxidant enzyme serving as a crucial negative regulator of ferroptosis, leading to the induction of ferroptosis through accumulation of lipid ROS. The iron chelator deferoxamine (DFO) alleviates EVO-induced cell death, G2/M cell cycle arrest, and lipid peroxidation via chelation of intracellular iron, which is essential for the execution of ferroptosis. In the TCCSUP tumor xenograft model, EVO inhibits tumor growth and suppresses EMT.