A novel peptide derived from human apolipoprotein E is an inhibitor of tumor growth and ocular angiogenesis

Angiogenesis is a hallmark of tumor development and metastasis and now a validated target for cancer treatment. We previously reported that a novel dimer peptide (apoEdp) derived from the receptor binding region of human apolipoprotein E (apoE) inhibits virus-induced angiogenesis. However, its role...

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Bibliographic Details
Published in:PloS one 2011-01, Vol.6 (1), p.e15905-e15905
Main Authors: Bhattacharjee, Partha S, Huq, Tashfin S, Mandal, Tarun K, Graves, Richard A, Muniruzzaman, Syed, Clement, Christian, McFerrin, Harris E, Hill, James M
Format: Article
Language:English
Subjects:
AKT protein
Analysis
Angiogenesis
Animals
Antineoplastic Agents - chemistry
Apolipoprotein E
Apolipoproteins
Apolipoproteins E - chemistry
Binding sites
Biology
Breast cancer
Cancer
Cancer therapies
Cancer treatment
Capillary tubes
Cell Movement - drug effects
Cell proliferation
Cell Proliferation - drug effects
Dipeptides - pharmacology
Drug therapy
Endothelial cells
Endothelium
Endothelium, Vascular - drug effects
Eye
Eye - blood supply
Eye - drug effects
Growth
Health sciences
Humans
In vivo methods and tests
Low density lipoprotein receptors
Medicine
Metastases
Metastasis
Mice
Mimicry
Neovascularization, Pathologic - drug therapy
Peptide Fragments - pharmacology
Peptides
Pharmacy
Phosphorylation
Prostate
Rabbits
Rodents
Signaling
Src protein
Studies
Umbilical vein
Umbilical Veins
Vascular endothelial growth factor
Vascular endothelial growth factor receptor 2
Viruses
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Summary:Angiogenesis is a hallmark of tumor development and metastasis and now a validated target for cancer treatment. We previously reported that a novel dimer peptide (apoEdp) derived from the receptor binding region of human apolipoprotein E (apoE) inhibits virus-induced angiogenesis. However, its role in tumor anti-angiogenesis is unknown. This study demonstrates that apoEdp has anti-angiogenic property in vivo through reduction of tumor growth in a mouse model and ocular angiogenesis in a rabbit eye model. Our in vitro studies show that apoEdp inhibits human umbilical vein endothelial cell proliferation, migration, invasion and capillary tube formation. We document that apoEdp inhibits vascular endothelial growth factor-induced Flk-1 activation as well as downstream signaling pathways that involve c-Src, Akt, eNOS, FAK, and ERK1/2. These in vitro data suggest potential sites of the apoE dipeptide inhibition that could occur in vivo.This is the first evidence that a synthetic dimer peptide mimicking human apoE has anti-angiogenesis functions and could be an anti-tumor drug candidate.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0015905