Cantharidin inhibits angiogenesis by suppressing VEGF-induced JAK1/STAT3, ERK and AKT signaling pathways.

Cantharidin (CTD), a chemical compound secreted by blister beetles, has been shown with anti-tumor property in many cancer cells. In this study, our data showed that CTD exerts potent anti-angiogenesis activity in a dose-dependent manner. CTD dose dependently suppressed human umbilical vascular endothelial cells proliferation, migration, and tube formation in vitro. Furthermore, CTD concentration dependently inhibited angiogenesis in chick embryo CAM model in vivo. At the molecular level, CTD abrogated VEGF-induced activation of STAT3 and suppressed the phosphorylation of JAK1 and ERK in a dose-dependent manner. Furthermore, CTD blocked the phosphorylation of AKT in a time-dependent manner. Taken together, these findings clearly demonstrate for the first time that CTD can inhibit angiogenesis and may have applications in the development of new anti-angiogenesis drugs.