Ellagic acid, a phenolic compound, exerts anti-angiogenesis effects via VEGFR-2 signaling pathway in breast cancer
Open Access
- 21 February 2012
- journal article
- research article
- Published by Springer Science and Business Media LLC in Breast Cancer Research and Treatment
- Vol. 134 (3), 943-955
- https://doi.org/10.1007/s10549-012-1977-9
Abstract
Anti-angiogenesis targeting VEGFR-2 has been considered as an important strategy for cancer therapy. Ellagic acid is a naturally existing polyphenol widely found in fruits and vegetables. It was reported that ellagic acid interfered with some angiogenesis-dependent pathologies. Yet the mechanisms involved were not fully understood. Thus, we analyzed its anti-angiogenesis effects and mechanisms on human breast cancer utilizing in-vitro and in-vivo methodologies. The in-silico analysis was also carried out to further analyze the structure-based interaction between ellagic acid and VEGFR-2. We found that ellagic acid significantly inhibited a series of VEGF-induced angiogenesis processes including proliferation, migration, and tube formation of endothelial cells. Besides, it directly inhibited VEGFR-2 tyrosine kinase activity and its downstream signaling pathways including MAPK and PI3K/Akt in endothelial cells. Ellagic acid also obviously inhibited neo-vessel formation in chick chorioallantoic membrane and sprouts formation of chicken aorta. Breast cancer xenografts study also revealed that ellagic acid significantly inhibited MDA-MB-231 cancer growth and P-VEGFR2 expression. Molecular docking simulation indicated that ellagic acid could form hydrogen bonds and aromatic interactions within the ATP-binding region of the VEGFR-2 kinase unit. Taken together, ellagic acid could exert anti-angiogenesis effects via VEGFR-2 signaling pathway in breast cancer.Keywords
This publication has 41 references indexed in Scilit:
- Hallmarks of Cancer: The Next GenerationCell, 2011
- Vascular endothelial growth factor receptor-2 in breast cancerBiochimica et Biophysica Acta (BBA) - Reviews on Cancer, 2010
- Novel angiogenesis inhibitory activity in cinnamon extract blocks VEGFR2 kinase and downstream signalingCarcinogenesis: Integrative Cancer Research, 2009
- Grape Seed Extract Inhibits Angiogenesis via Suppression of the Vascular Endothelial Growth Factor Receptor Signaling PathwayCancer Prevention Research, 2008
- Immunohistochemistry in the evaluation of neovascularization in tumor xenograftsBiotechnic & Histochemistry, 2008
- Breast tumour angiogenesisBreast Cancer Research, 2007
- Mechanisms of adverse effects of anti-VEGF therapy for cancerBritish Journal of Cancer, 2007
- Vascular Endothelial Growth Factor and AngiogenesisPublished by American Society for Pharmacology & Experimental Therapeutics (ASPET) ,2004
- Saikosaponin C induces endothelial cells growth, migration and capillary tube formationLife Sciences, 2004
- The biology of VEGF and its receptorsNature Medicine, 2003