VEGFA and cancer: Other mechanisms that have been related to metformin as an anti-cancer drug are the activation of factors that inhibit the cell cycle (p53, p21, cyclin D1) as well as cell proliferation, which induces apoptosis [22,24], the suppression of hypoxia-inducible factor (HIF)-1 and vascular endothelial growth factor (VEGF), making cancer cells more susceptible to hypoxic environments, metastasis, and wrong angiogenesis development [25].