Antiangiogenic effect of pinobanksin on human umbilical vein endothelial cells

Abstract

• Pinobanksin inhibits the tube formation and migration of HUVECs. • Pinobanksin exhibits antiangiogenic effect by inducing endothelial cell apoptosis. • Pinobanksin suppresses new blood vessel growth of chick embryos. • Pinobanksin reduces the MEK/ERK activation and inhibits the cell adhesion molecules. Propolis is a resinous material that is collected by bees from buds and bark. Previously, we have reported that propolis possesses antiangiogenic activities. However, the mechanism of angiogenesis inhibition by pinobanksin, the main component of propolis, has not been well-clarified. In this study, we examine the antiangiogenic potential of pinobanksin in both in vitro and in vivo assays. We analyze the effects of pinobanksin on cell migration, apoptosis, and angiogenesis of human umbilical vein endothelial cells. We find that inhibition of tube formation by pinobanksin induces apoptosis with the partial fragmentation of endothelial cells. The results of Western blotting reveal the mechanism that pinobanksin-induced inhibition of angiogenesis is implicated as being mediated via inactivation of the Raf/MEK/ERK pathway and activation of apoptotic signaling such as caspase cascades. These results suggest that pinobanksin exhibits antiangiogenic effect by inducing endothelial cell apoptosis, and that pinobanksin can be developed as an antiangiogenic agent.