Design and Development of Peptides from the Anti-Angiogenic Pigment Epithelial-Derived Factor for the Therapy of Prostate Cancer
Abstract
To create PEDF based therapy for hormone-refractory CaP we have proposed to design short synthetic peptides corresponding to the 34- mer anti-angiogenic epitope of PEDF. The 3D structure of PEDF 34-mer peptide was analyzed using Protean software in terms of relative hydrophobicity, charge distribution, and antigenic index. Three synthetic peptides covering the 34-mer PEDF fragment were generated and tested for the ability to reproduce anti-angiogenic effect of PEDF. Although all peptides (14, 18 and 23-mer) inhibited FGF-induced endothelial cell migration only 18 and 23-mer induced apoptosis in endothelial cells. The 18-mer peptide also blocked neovascularization induced by FGF in vivo as demonstrated in corneal and matrigel assays. This peptide was further tested in vivo in mouse model for ability to inhibit prostate tumor growth. Subcutaneous PC3 tumor growth was inhibited in mice treated with 18-mer peptide. There was significant reduction in microvascular density in the 18-mer treated animals accompanied by increased apoptosis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2007
- Accession Number
- ADA477451
Entities
People
- Yelena Mirochnik
Organizations
- Northwestern University