FOXO3 and breast carcinoma: Interestingly, Hou et al. demonstrated that metformin inhibited intracellular ROS by upregulation of Trx expression via the AMPK-FOXO3 pathway in human aortic endothelial cells [31], whilst the current study shows the opposite in breast cancer MCF7 cells, with metformin increasing ROS production by decreasing Trx expression.