Myricetin Inhibits Angiogenesis by Inducing Apoptosis and Suppressing PI3K/Akt/mTOR Signaling in Endothelial Cells

ABSTRACT

BACKGROUND: Myricetin has been shown to possess potential antiangiogenic effects in endothelial cells. However, the underlying mechanisms are not fully understood. Therefore, we evaluated its antiangiogenic effects in human umbilical vascular endothelial cells (HUVECs). METHODS: HUVECs were cultured in endothelial cell growth medium-2 to induce proliferation and angiogenesis and treated with different doses of myricetin (0.25, 0.5, and 1 μM) for 24 hours. Cell proliferation was analyzed by the MTT and lactate dehydrogenase release assays; angiogenesis was determined by the tube formation assay. In addition, cell signaling pathways related to angiogenesis were investigated by Western blotting. RESULTS: Myricetin induced apoptosis and procaspase-3 cleavage though the induction of reactive oxygen species (ROS). It significantly inhibited cell migration, tube formation, and PI3K/Akt/mTOR signaling in HUVECs. CONCLUSIONS: Myricetin exerts antiangiogenic effects by inducing ROS-mediated apoptosis and inhibiting PI3K/Akt/mTOR signaling in HUVECs.