Kaempferol inhibits angiogenic ability by targeting VEGF receptor-2 and downregulating the PI3K/AKT, MEK and ERK pathways in VEGF-stimulated human umbilical vein endothelial cells.

Anti-angiogenesis is one of the most general clinical obstacles in cancer chemotherapy. Kaempferol is a flavonoid phytochemical found in many fruits and vegetables. Our previous study revealed that kaempferol triggered apoptosis in human umbilical vein endothelial cells (HUVECs) by ROS­mediated p53/ATM/death receptor signaling. However, the anti­angiogenic potential of kaempferol remains unclear and its underlying mechanism warranted further exploration in VEGF­stimulated HUVECs. In the present study, kaempferol significantly reduced VEGF­stimulated HUVEC viability. Kaempferol treatment also inhibited cell migration, invasion, and tube formation in VEGF­stimulated HUVECs. VEGF receptor­2 (VEGFR­2), and its downstream signaling cascades (such as AKT, mTOR and MEK1/2­ERK1/2) were reduced as determined by western blotting and kinase activity assay in VEGF­stimulated HUVECs after treatment with kaempferol. The present study revealed that kaempferol may possess angiogenic inhibition through regulation of VEGF/VEGFR­2 and its downstream signaling cascades (PI3K/AKT, MEK and ERK) in VEGF-stimulated endothelial cells.