Page 44 - I. Chemical biology and drug discovery

[I. Chemical biology and drug discovery-23]

Berbamine inhibits BDNF-induced angiogenesis of HUVECs in

vitro and in vivo

Yu Jin Kim¹, Jang Mi Han¹, Hye Jin Jung¹˙*

¹Pharmaceutical Engineering & Biotechnology, Sun Moon University, Asan 31460, Korea

Brain-derived neurotrophic factor (BDNF), a neurotrophin, plays a critical role in neural development through the
activation of its specific receptor, tropomyosin-related kinase B (TrkB). Recent reports have revealed that BDNF can
promote angiogenesis and thus contributes to growth and metastasis of numerous tumor types. Although

berbamine, a natural compound from the plant Berberis amurensis, is known to exert an anticancer activity by

targeting Ca2+/calmodulin-dependent protein kinase II (CaMKII), its antiangiogenic activity in endothelial cells has
been not identified. We here investigated the effect of berbamine on angiogenesis stimulated by BDNF. As a result,
berbamine effectively suppressed the BDNF-induced angiogenic phenotypes such as proliferation, invasion, tube

formation, and adhesion of human umbilical vein endothelial cells (HUVECs) without exhibiting cytotoxicity. In
addition, it potently inhibited the neovascularization of chorioallantoic membrane of growing chick embryo in the

presence of BDNF. The antiangiogenic effect of berbamine was also associated with the downregulation of ROS
generation increased by BDNF. The molecular mechanism study to identify the role of BDNF/TrKB/CaMKII axis in

the antiangiogenic effect of berbamine is currently underway.