Dietary Compound Isoliquiritigenin Inhibits Breast Cancer Neoangiogenesis via VEGF/VEGFR-2 Signaling Pathway
Open Access
- 5 July 2013
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 8 (7), e68566
- https://doi.org/10.1371/journal.pone.0068566
Abstract
Angiogenesis is crucial for cancer initiation, development and metastasis. Identifying natural botanicals targeting angiogenesis has been paid much attention for drug discovery in recent years, with the advantage of increased safety. Isoliquiritigenin (ISL) is a dietary chalcone-type flavonoid with various anti-cancer activities. However, little is known about the anti-angiogenic activity of isoliquiritigenin and its underlying mechanisms. Herein, we found that ISL significantly inhibited the VEGF-induced proliferation of human umbilical vein endothelial cells (HUVECs) at non-toxic concentration. A series of angiogenesis processes including tube formation, invasion and migration abilities of HUVECs were also interrupted by ISL in vitro. Furthermore, ISL suppressed sprout formation from VEGF-treated aortic rings in an ex-vivo model. Molecular mechanisms study demonstrated that ISL could significantly inhibit VEGF expression in breast cancer cells via promoting HIF-1α (Hypoxia inducible factor-1α) proteasome degradation and directly interacted with VEGFR-2 to block its kinase activity. In vivo studies further showed that ISL administration could inhibit breast cancer growth and neoangiogenesis accompanying with suppressed VEGF/VEGFR-2 signaling, elevated apoptosis ratio and little toxicity effects. Molecular docking simulation indicated that ISL could stably form hydrogen bonds and aromatic interactions within the ATP-binding region of VEGFR-2. Taken together, our study shed light on the potential application of ISL as a novel natural inhibitor for cancer angiogenesis via the VEGF/VEGFR-2 pathway. Future studies of ISL for chemoprevention or chemosensitization against breast cancer are thus warranted.Keywords
This publication has 48 references indexed in Scilit:
- Ellagic acid, a phenolic compound, exerts anti-angiogenesis effects via VEGFR-2 signaling pathway in breast cancerBreast Cancer Research and Treatment, 2012
- Differential Effects of VEGFR-1 and VEGFR-2 Inhibition on Tumor Metastases Based on Host Organ EnvironmentCancer Research, 2010
- The Four-Herb Chinese Medicine PHY906 Reduces Chemotherapy-Induced Gastrointestinal ToxicityScience Translational Medicine, 2010
- Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs): Positive and negative regulators in tumor cell adhesionSeminars in Cancer Biology, 2010
- Cancer Chemopreventive Activity and Metabolism of Isoliquiritigenin, a Compound Found in LicoriceCancer Prevention Research, 2010
- Adenovirus-mediated transfer of siRNA against MMP-2 mRNA results in impaired invasion and tumor-induced angiogenesis, induces apoptosis in vitro and inhibits tumor growth in vivo in glioblastomaOncogene, 2008
- PI3K/PTEN/AKT signaling regulates prostate tumor angiogenesisCellular Signalling, 2007
- VEGF receptor signalling ? in control of vascular functionNature Reviews Molecular Cell Biology, 2006
- Role of the Vascular Endothelial Growth Factor Pathway in Tumor Growth and AngiogenesisJournal of Clinical Oncology, 2005
- Failure of blood-island formation and vasculogenesis in Flk-1-deficient miceNature, 1995