FOXO3 and pancreatic neoplasm: Warkad et al. also reported that metformin differentially regulates cellular ROS levels through the AMPK-FOXO3a, forkhead box O3a (FOXO3a)-MnSOD pathways in AsPC-1 pancreatic cancer cells and that the combination of metformin and apigenin induces DNA damage by AsPC-1 pancreatic cancer cell-specific ROS amplification, which results in apoptosis, autophagy, and necroptosis.