Anti-angiogenic effects of Siegesbeckia glabrescens are mediated by suppression of the Akt and p70S6K-dependent signaling pathways

Siegesbeckia glabrescens (SG) Makino (Compositae) has been used as a traditional medicine for the treatment of allergic and inflammatory diseases. In the present study, we report the effects and molecular mechanism of an ethanolic extract of SG on cell proliferation, migration and tube formation in vascular endothelial growth factor-A (VEGF-A)-treated human umbilical vein endothelial cells. SG treatment inhibited VEGF-A-stimulated endothelial cell proliferation through downregulation of cyclin D and upregulation of cyclin-dependent kinase inhibitors such as p27(Kip1) and p21(WAF1/Cip1). In addition, SG inhibited VEGF-A-stimulated endothelial cell migration and tube formation. These anti-angiogenic activities of SG were mediated by inactivation of the Akt- and p70(S6K)-dependent signaling pathways. Collectively, our findings demonstrate the pharmacological roles and molecular mechanism of SG in regulating angiogenic responses and support further evaluation and development of SG as a potential therapeutic agent for the treatment and prevention of angiogenesis-related diseases including cancer.