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Novel antiangiogenic peptides inhibit tumor growth in breast cancer xenografts
Author(s) -
Koskimaki Jacob E,
Rosca Elena,
Raman Venu,
Bhujwalla Zaver,
Popel Aleksander
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.761.1
Subject(s) - angiogenesis , in vivo , cancer research , breast cancer , neovascularization , cancer , in vitro , cell growth , peptide , oligopeptide , cancer cell , umbilical vein , biology , medicine , biochemistry , microbiology and biotechnology
Breast cancer is the most commonly diagnosed female malignancy in the United States, proving fatal to nearly 40,000 people in 2007. Angiogenesis or neovascularization, the process of new blood vessel formation from pre‐existing microvasculature, is necessary for homeostasis in tissue, and tumor progression. We previously introduced a novel systematic methodology to identify putative endogenous antiangiogenic peptides and validated these predictions in vitro in human umbilical vein endothelial cell (HUVEC) proliferation and migration assays, and have evaluated the ability of several peptides to suppress angiogenesis in breast cancer orthotopic xenograft models in severe combined immunodeficient (SCID) mice using MDA‐MB‐231 human breast cancer cells. Peptides were administered intraperitoneally, once per day, and tested at several concentrations. After demonstrating significant suppression of tumor growth in vivo with unmodified sequences, we have modified peptides using synthetic amino acids to replace cysteines with {alpha}‐amino‐n‐butyric acid (Abu). Using these peptide modifications, we have shown peptide bioactivity in vitro in cell proliferation assays and significant suppression of tumor growth in vivo. These modified sequences are stable under oxidizing conditions, and represent significant steps towards translational clinical research.