The direct anticancer effects of metformin are essentially mediated by AMPK-dependent (decreasing mTOR, c-MYC and NFκB, and increasing p53 phosphorylation) and AMPK-independent (decreasing ROS, increasing mTORC1, decreasing cyclin D1, increasing autophagy and apoptosis of cancer cells) mechanisms [32,33]. Here, TP53 is linked to cancer.