Antiangiogenic and apoptotic effects of benzyl caffeate on human umbilical vein endothelial cells (HUVECs) and chick embryo chorioallantoic membrane (CAM): In vitro and in vivo models

Caffeic acid and its derivatives are polyphenolic compounds, which are present in high concentration in propolis and medicinal plants. Their antioxidant activity has been reported; however, the antiangiogenic effects of benzyl caffeate remain unclear. In this study, we investigated the angiogenic and apoptotic effects of benzyl caffeate both in vitro on HUVECs and in vivo in chick embryo chorionic membrane (CAM) models. Benzyl caffeate significantly inhibited angiogenesis via HUVECs-based tube formation by inducing apoptosis and anti proliferative effects on endothelial cells. Furthermore, benzyl caffeate significantly reduced the number of newly formed vessels in CAM. Western blot analysis showed that benzyl caffeate induced apoptosis via proapototic signaling via activation of caspase-9, caspase-3 and cleavage of PARP and lamin A/C. In addition, western blot showed that benzyl caffeate treatment inhibited c-Raf/MEK/ERK signaling, and thereby suppressed angiogenesis. In conclusion, the results indicate that benzyl caffeate exerts its antiangiogenic effects via induction of endothelial apoptosis.