HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Barbigerone, an isoflavone, inhibits tumor angiogenesis and human non-small-cell lung cancer xenografts growth through VEGFR2 signaling pathways.

AbstractPURPOSE:
We previously reported that barbigerone (BA), an isoflavone isolated from Suberect Spatholobus, exhibited inhibitory effects on proliferation of many cancer cell lines in vitro. The objective of this study was to explore whether BA could effectively suppress tumor angiogenesis and tumor growth.
METHODS:
Zebrafish model and Matrigel assay were performed to access the anti-angiogenesis effects of BA. A549 and SPC-A1 tumor xenografts in mice models were used to examine the antitumor activity of BA. The anti-angiogenic effects and underlying mechanisms were also investigated using human umbilical vein endothelial cells (HUVECs) and A549 cells.
RESULTS:
In zebrafish model, 2.5 μmol/L of BA significantly inhibited angiogenesis. Intravenous administration of BA effectively inhibited the tumor growth of A549 and SPC-A1 xenograft models in mice. The anti-angiogenic effect was indicated by CD31 immunohistochemical staining, Matrigel plug assay, and mouse aortic ring assay. BA could inhibit vascular endothelial growth factor (VEGF)-induced cell proliferation, migration, and capillary-like tuber formation of HUVECs in a dose-dependent manner, suggesting that BA inhibited tumorigenesis by targeting angiogenesis. Western blots revealed that BA directly inhibited the phosphorylation of VEGFR2, followed by inhibiting the activations of its downstream protein kinases, including ERK, p38, FAK, AKT, and expression of iNOS, but had no effect on COX2. Additionally, BA could also down-regulate VEGF secretion in A549 cancer cells, which may correlate with the suppression of ERK, AKT activation, indicating that BA inhibits tumor angiogenesis and tumor growth through VEGFR2 signaling pathways.
CONCLUSIONS:
These findings suggest that BA may be a novel candidate in inhibiting tumor angiogenesis and NSCLC tumor growth.
AuthorsXiuxia Li, Xuewei Wang, Haoyu Ye, Aihua Peng, Lijuan Chen
JournalCancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 70 Issue 3 Pg. 425-37 (Sep 2012) ISSN: 1432-0843 [Electronic] Germany
PMID22814678 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Angiogenesis Inhibitors
  • Drug Combinations
  • Isoflavones
  • Laminin
  • Proteoglycans
  • barbigerone
  • matrigel
  • Collagen
  • Vascular Endothelial Growth Factor Receptor-2
Topics
  • Angiogenesis Inhibitors (administration & dosage, pharmacology)
  • Animals
  • Carcinoma, Non-Small-Cell Lung (blood supply, drug therapy, pathology)
  • Cell Movement (drug effects)
  • Cell Proliferation (drug effects)
  • Collagen (metabolism)
  • Dose-Response Relationship, Drug
  • Drug Combinations
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Isoflavones (administration & dosage, pharmacology)
  • Laminin (metabolism)
  • Lung Neoplasms (blood supply, drug therapy, pathology)
  • Mice
  • Mice, Inbred C57BL
  • Mice, Nude
  • Neovascularization, Pathologic (drug therapy)
  • Proteoglycans (metabolism)
  • Signal Transduction (drug effects)
  • Vascular Endothelial Growth Factor Receptor-2 (antagonists & inhibitors)
  • Xenograft Model Antitumor Assays
  • Zebrafish

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: