Tumor growth depends on angiogenesis and inducing angiogenesis is one of the most important hallmarks in the
cancer development. Treatment with small molecules that inhibit angiogenesis has been an effective strategy for anti-
cancer therapy. Some anti-angiogenic factors are derived from traditional Chinese herbs.
Usnic acid (UA), an active compound mainly found in lichens, has shown some
biological and physiological activities. However, the role and mechanism of UA in
tumor angiogenesis are still unknown. The aim of this study was to assess the effects of UA on
tumor angiogenesis. In this study, we demonstrated that UA strongly inhibited in vivo angiogenesis in a chick embryo chorioallantoic membrane assay and
vascular endothelial growth factor-induced mouse
corneal angiogenesis model. In a mouse xenograft
tumor model, UA suppressed Bcap-37
breast tumor growth and angiogenesis without affecting mice
body weight. In an in vitro assay, UA not only significantly inhibited endothelial cell proliferation, migration and tube formation, but also induced morphological changes and apoptosis in endothelial cells. In addition, UA inhibited Bcap-37
tumor cell proliferation. Moreover, western blot analysis of cell signaling molecules indicated that UA blocked
vascular endothelial growth factor receptor (VEGFR) 2 mediated Extracellular signal-regulated
protein kinases 1 and 2(ERK1/2) and AKT/
P70S6K signaling pathways in endothelial cells. These results provided the first evidence of the
biological function and molecular mechanism of UA in
tumor angiogenesis.