PUBLICATION
Novel PI3K/AKT targeting anti-angiogenic activities of 4-vinylphenol, a new therapeutic potential of a well-known styrene metabolite
- Authors
- Yue, G.G., Lee, J.K., Kwok, H.F., Cheng, L., Wong, E.C., Jiang, L., Yu, H., Leung, H.W., Wong, Y.L., Leung, P.C., Fung, K.P., Lau, C.B.
- ID
- ZDB-PUB-150609-1
- Date
- 2015
- Source
- Scientific Reports 5: 11149 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Angiogenesis Inhibitors/pharmacology*
- Animals
- Cell Adhesion/drug effects
- Cell Line, Tumor
- Cell Movement/drug effects
- Cell Proliferation/drug effects
- Cyclin B1/metabolism
- Cyclin D1/metabolism
- Down-Regulation
- Drugs, Chinese Herbal/pharmacology
- Extracellular Matrix Proteins/metabolism
- Extracellular Signal-Regulated MAP Kinases/metabolism
- Female
- Hedyotis/metabolism
- Human Umbilical Vein Endothelial Cells/drug effects
- Humans
- MAP Kinase Signaling System/drug effects
- Male
- Matrix Metalloproteinase 2/biosynthesis
- Mice
- Mice, Inbred BALB C
- Mice, Inbred C57BL
- NF-kappa B/biosynthesis
- Neovascularization, Pathologic/drug therapy*
- Phenols/pharmacology*
- Phosphatidylinositol 3-Kinases/metabolism*
- Phosphorylation/drug effects
- Plant Extracts/pharmacology
- Proto-Oncogene Proteins c-akt/metabolism*
- Styrenes/metabolism
- Vascular Endothelial Growth Factor Receptor-1/biosynthesis
- Vascular Endothelial Growth Factor Receptor-2/biosynthesis
- Zebrafish
- p38 Mitogen-Activated Protein Kinases/metabolism
- PubMed
- 26053458 Full text @ Sci. Rep.
Citation
Yue, G.G., Lee, J.K., Kwok, H.F., Cheng, L., Wong, E.C., Jiang, L., Yu, H., Leung, H.W., Wong, Y.L., Leung, P.C., Fung, K.P., Lau, C.B. (2015) Novel PI3K/AKT targeting anti-angiogenic activities of 4-vinylphenol, a new therapeutic potential of a well-known styrene metabolite. Scientific Reports. 5:11149.
Abstract
The pneumo- and hepato-toxicity of 4-vinylphenol (4VP), a styrene metabolite, has been previously reported. Nevertheless, the present study reported the novel anti-angiogenic activities of 4VP which was firstly isolated from the aqueous extract of a Chinese medicinal herb Hedyotis diffusa. Our results showed that 4VP at non-toxic dose effectively suppressed migration, tube formation, adhesion to extracellular matrix proteins, as well as protein and mRNA expressions of metalloproteinase-2 of human endothelial cells (HUVEC and HMEC-1). Investigation of the signal transduction revealed that 4VP down-regulated PI3K/AKT and p38 MAPK. Besides, 4VP interfered with the phosphorylation of ERK1/2, the translocation and expression of NFkappaB. In zebrafish embryo model, the new blood vessel growth was significantly blocked by 4VP (6.25-12.5 μg/mL medium). The VEGF-induced blood vessel formation in Matrigel plugs in C57BL/6 mice was suppressed by 4VP (20-100 μg/mL matrigel). In addition, the blood vessel number and tumor size were reduced by intraperitoneal 4VP (0.2-2 mg/kg) in 4T1 breast tumor-bearing BALB/c mice, with doxorubicin as positive control. Together, the in vitro and in vivo anti-angiogenic activities of 4VP were demonstrated for the first time. These findings suggest that 4VP has great potential to be further developed as an anti-angiogenic agent.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping