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ZIRC
ZFIN ID: ZDB-PUB-140502-21
Barbigerone inhibits tumor angiogenesis, growth and metastasis in melanoma
Yang, J.H., Hu, J., Wan, L., and Chen, L.J.
Date: 2014
Source: Asian Pacific journal of cancer prevention : APJCP   15(1): 167-174 (Journal)
Registered Authors: Hu, Jia
Keywords: none
MeSH Terms:
  • Angiogenesis Inhibitors/pharmacology
  • Angiogenesis Inhibitors/therapeutic use*
  • Animals
  • Cell Movement/drug effects
  • Cell Proliferation/drug effects
  • Focal Adhesion Kinase 1/metabolism
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Isoflavones/pharmacology
  • Isoflavones/therapeutic use*
  • Lung Neoplasms/prevention & control*
  • Lung Neoplasms/secondary
  • Melanoma, Experimental/blood supply*
  • Melanoma, Experimental/drug therapy
  • Melanoma, Experimental/pathology
  • Melanoma, Experimental/secondary
  • Mice
  • Mice, Inbred C57BL
  • Microvessels/drug effects
  • Microvessels/pathology
  • Mitogen-Activated Protein Kinases/metabolism*
  • Neovascularization, Pathologic/drug therapy*
  • Phosphorylation/drug effects
  • Platelet Endothelial Cell Adhesion Molecule-1/analysis
  • Proto-Oncogene Proteins c-akt/metabolism
  • Signal Transduction/drug effects
  • Tumor Cells, Cultured
  • Zebrafish
PubMed: 24528020 Full text @ Asian Pac. J. Cancer Prev.
ABSTRACT

Tumor angiogenesis, growth and metastasis are three closely related processes. We therefore investigated the
effects of barbigerone on all three in the B16F10 tumor model established in both zebrafish and mouse models,
and explored underlying molecular mechanisms. In vitro, barbigerone inhibited B16F10 cell proliferation,
survival, migration and invasion and suppressed human umbilical vascular endothelial cell migration, invasion
and tube formation in concentration-dependent manners. In the transgenic zebrafish model, treatment with
10µM barbigerone remarkably inhibited angiogenesis and tumor-associated angiogenesis by reducing blood vessel
development more than 90%. In vivo, barbigerone significantly suppressed angiogenesis as measured by H and
E staining of matrigel plugs and CD31 staining of B16F10 melanoma tumors in C57BL/6 mice. Furthermore,
it exhibited highly potent activity at inhibiting tumor growth and metastasis to the lung of B16F10 melanoma
cells injected into C57BL/6 mice. Western blotting revealed that barbigerone inhibited phosphorylation of AKT,
FAK and MAPK family members, including ERK, JNK, and p38 MAPKs, in B16F10 cells mainly through the
MEK3/6/p38 MAPK signaling pathway. These findings suggested for the first time that barbigerone could inhibit
tumor-angiogenesis, tumor growth and lung metastasis via downregulation of the MEK3/6/p38 MAPK signaling
pathway. The findings support further investigation of barbigerone as a potential anti-cancer drug.

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