ANG and neoplasm: Even the endothelial cell model adapted in this manuscript is not representative for tumor angiogenesis in vivo; many studies have described the anti-angiogenic activity of metformin in tumor models with the involvement of abundant numbers of angiogenesis-associated proteins such as VEGF45,46, cyclooxygenase 2, CXC chemokine receptor 4, IL-8, angiogenin, and TIMP-147.