Pharmacoproteomic analysis of a novel cell-permeable peptide inhibitor of tumor-induced angiogenesis.
Mol Cell Proteomics
; 10(8): M110.005264, 2011 Aug.
Article
em En
| MEDLINE
| ID: mdl-21558493
ABSTRACT
P11, a novel peptide ligand containing a PDZ-binding motif (Ser-Asp-Val) with high affinity to integrin α(v)ß(3) was identified from a hexapeptide library (PS-SPCL) using a protein microarray chip-based screening system. Here, we investigated the inhibitory mechanism of P11 (HSDVHK) on tumor-induced angiogenesis via a pharmacoproteomic approach. P11 was rapidly internalized by, human umbilical vein endothelial cells (HUVECs) via an integrin α(v)ß(3)-mediated event. Caveolin and clathrin appeared to be involved in the P11 uptake process. The cell-penetrating P11 resulted in suppression of bFGF-induced HUVEC proliferation in a dose-dependent manner. Phosphorylation of extracellular-signal regulated kinase (ERK1/2) and mitogen-activated protein kinase kinase (MEK) in bFGF-stimulated HUVECs was inhibited by cell-permeable P11. Proteomic analysis via antibody microarray showed up-regulation of p53 in P11-treated HUVECs, resulting in induction of apoptosis via activation of caspases-3, -8, and -9. Several lines of experimental evidence strongly suggest that the molecular mechanism of P11, a novel anti-angiogenic agent, inhibits bFGF-induced HUVEC proliferation via mitogen-activated protein kinase kinase and extracellular-signal regulated kinase inhibition as well as p53-mediated apoptosis related with activation of caspases.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proliferação de Células
/
Peptídeos Penetradores de Células
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Neovascularização Patológica
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Mol Cell Proteomics
Ano de publicação:
2011
Tipo de documento:
Article