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Novel PI3K/AKT targeting anti-angiogenic activities of 4-vinylphenol, a new therapeutic potential of a well-known styrene metabolite
Yue G.G.-L.; Lee J.K.-M.; Kwok H.-F.; Cheng L.; Wong E.C.-W.; Jiang L.; Yu H.; Leung H.-W.; Wong Y.-L.; Leung P.-C.; Fung K.-P.; Lau C.B.-S.
2015-06-08
Source PublicationScientific Reports
ISSN20452322
Volume5
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 (6.25-12.5â €‰Î 1/4g/mL medium). The VEGF-induced blood vessel formation in Matrigel plugs in C57BL/6 mice was suppressed by 4VP (20-100â €‰Î 1/4g/mL matrigel). In addition, the blood vessel number and tumor size were reduced by intraperitoneal 4VP (0.2-2â €‰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.

DOI10.1038/srep11149
URLView the original
Indexed BySCI
Language英语
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000356071100002
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Cited Times [WOS]:18   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
AffiliationChinese University of Hong Kong
Recommended Citation
GB/T 7714
Yue G.G.-L.,Lee J.K.-M.,Kwok H.-F.,et al. Novel PI3K/AKT targeting anti-angiogenic activities of 4-vinylphenol, a new therapeutic potential of a well-known styrene metabolite[J]. Scientific Reports,2015,5.
APA Yue G.G.-L..,Lee J.K.-M..,Kwok H.-F..,Cheng L..,Wong E.C.-W..,...&Lau C.B.-S..(2015).Novel PI3K/AKT targeting anti-angiogenic activities of 4-vinylphenol, a new therapeutic potential of a well-known styrene metabolite.Scientific Reports,5.
MLA Yue G.G.-L.,et al."Novel PI3K/AKT targeting anti-angiogenic activities of 4-vinylphenol, a new therapeutic potential of a well-known styrene metabolite".Scientific Reports 5(2015).
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