Novel PI3K/AKT targeting anti-angiogenic activities of 4-vinylphenol, a new therapeutic potential of a well-known styrene metabolite
| Autor: | Ling Cheng, Clara Bik-San Lau, Yuk-Lau Wong, Ping-Chung Leung, Julia Kin-Ming Lee, Grace Gar-Lee Yue, Eric Chun-Wai Wong, Hua Yu, Hoi-Wing Leung, Lei Jiang, Kwok-Pui Fung, Hin-Fai Kwok |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Metabolite Angiogenesis Inhibitors p38 Mitogen-Activated Protein Kinases Hedyotis diffusa Mice Phosphatidylinositol 3-Kinases chemistry.chemical_compound Cell Movement Cyclin D1 Phosphorylation Extracellular Signal-Regulated MAP Kinases Zebrafish Tube formation Extracellular Matrix Proteins Mice Inbred BALB C Multidisciplinary Neovascularization Pathologic NF-kappa B medicine.anatomical_structure Matrix Metalloproteinase 2 Female Blood vessel MAP Kinase Signaling System Down-Regulation Biology Article Styrenes Phenols In vivo Cell Line Tumor Cell Adhesion Hedyotis Human Umbilical Vein Endothelial Cells medicine Animals Humans Cyclin B1 Protein kinase B PI3K/AKT/mTOR pathway Cell Proliferation Matrigel Vascular Endothelial Growth Factor Receptor-1 Plant Extracts biology.organism_classification Vascular Endothelial Growth Factor Receptor-2 Molecular biology Mice Inbred C57BL chemistry Proto-Oncogene Proteins c-akt Drugs Chinese Herbal |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep11149 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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