Artepillin C Suppresses Angiogenesis by Inhibiting Tube-Formation and Inducing Apoptosis of Endothelial Cells

Mok-Ryeon Ahn^1, , Sun Wook Kim², Shigenori Kumazawa³ and Toshiro Ohta³

¹Department of Food Science and Nutrition, Dong-A University, Busan, Republic of Korea

²Department of Molecular and Cellular Physiology, University of Cincinnati, Cincinnati, OH, USA

³Department of Food and Nutritional Sciences, University of Shizuoka, Shizuoka, Japan

Cite this paper:
Mok-Ryeon Ahn, Sun Wook Kim, Shigenori Kumazawa and Toshiro Ohta. Artepillin C Suppresses Angiogenesis by Inhibiting Tube-Formation and Inducing Apoptosis of Endothelial Cells. Journal of Food and Nutrition Research. 2013; 1(5):92-96. doi: 10.12691/jfnr-1-5-3

Abstract

Artepillin C (ARC) is a major active ingredient of Brazilian propolis which is a resinous mixed compound collected by honeybeesfrom various plant sources. Previously, we reported that the ethanol extract of Brazilian propolis possesses antiangiogenic activity both in vitro and in vivo. However, the mechanism of angiogenesis inhibitionby purified ARC has not been well-clarified. In this study, we investigated the effects of ARC on tube-forming human umbilical vein endothelial cells (HUVECs). We found that inhibition of tube formation by ARC was accompanied by partial fragmentation of endothelial cells, indicating that it induced cell death. Western blotting revealed that ARC induced the reduction of vascular endothelial cadherinand platelet endothelial cell adhesion molecule-1. ARC also induced chromatin condensation and cell nuclear fragmentation, morphological markers of apoptosis, in tube-forming HUVECs. Furthermore, ARC suppressed phosphorylation of extracellular signal-regulated kinase 1/2, but upregulated phosphorylation of p38. It was also shown that ARC induced apoptosis via activation of proapototic signaling, activation of caspase-3 and cleavage of poly ADP-ribose polymerase and lamin A/C. In conclusion, ARC exerts its antiangiogenic effects through induction of endothelial apoptosis.

Keywords:
angiogenesis apoptosis artepillin C endothelial cell tube formation

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