Pegylated Recombinant Human Arginase 1 Induces Autophagy and Apoptosis via the ROS-Activated AKT/mTOR Pathway in Bladder Cancer Cells

Bladder cancer is one of the most commonly diagnosed cancers worldwide, especially in males. Current therapeutic interventions, including surgery, radiation therapy, chemotherapy, and immunotherapy, have not been able to improve clinical outcome bladder patients with satisfaction. Recombinant human arginase (rhArg, BCT-100) a novel agent great anticancer effects on arginine-auxotrophic tumors. However, BCT-100 remain unclear. In this study, vitro were assessed using four cell lines (J82, SCaBER, T24, 5637), while vivo evaluated by establishing T24 nude mice xenograft models. Intracellular arginine level was observed be sharply decreased followed onset apoptotic events. Furthermore, found induce H2O2 production mitochondrial membrane depolarization, leading release cytochrome c Smac cytosol. Treatment BCT upregulate expression LC3B Becllin-1, but downregulate p62 time-dependent manner. Autophagic flux also upon treatment. Besides, phosphorylation AKT/mTOR pathway suppressed fashion BCT-100-treated cells. While N-acetyl-L-cysteine shown alleviate BCT-100-induced apoptosis autophagy, chloroquine, MK-2206, rapamycin potentiate BCT-100-triggered apoptosis. Finally, demonstrated autophagy via ROS-mediated signaling