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

Oncol Rep. 2018 May;39(5):2351-2357. doi: 10.3892/or.2018.6312. Epub 2018 Mar 14.

Abstract

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 ROS‑mediated p53/ATM/death receptor signaling. However, the anti‑angiogenic potential of kaempferol remains unclear and its underlying mechanism warranted further exploration in VEGF‑stimulated HUVECs. In the present study, kaempferol significantly reduced VEGF‑stimulated HUVEC viability. Kaempferol treatment also inhibited cell migration, invasion, and tube formation in VEGF‑stimulated HUVECs. VEGF receptor‑2 (VEGFR‑2), and its downstream signaling cascades (such as AKT, mTOR and MEK1/2‑ERK1/2) were reduced as determined by western blotting and kinase activity assay in VEGF‑stimulated HUVECs after treatment with kaempferol. The present study revealed that kaempferol may possess angiogenic inhibition through regulation of VEGF/VEGFR‑2 and its downstream signaling cascades (PI3K/AKT, MEK and ERK) in VEGF-stimulated endothelial cells.

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Down-Regulation
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Kaempferols / pharmacology*
  • MAP Kinase Signaling System / drug effects*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism
  • Vascular Endothelial Growth Factor A / pharmacology*
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism*

Substances

  • Angiogenesis Inhibitors
  • Kaempferols
  • Vascular Endothelial Growth Factor A
  • kaempferol
  • Phosphatidylinositol 3-Kinases
  • KDR protein, human
  • Vascular Endothelial Growth Factor Receptor-2
  • Proto-Oncogene Proteins c-akt