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