Journal
ONCOTARGET
Volume 5, Issue 4, Pages 901-907Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.1809
Keywords
prostate cancer; penetratin-peptide; Du-145 cells
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Funding
- Lung Cancer Foundation
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E2F-1, a key transcription factor necessary for cell growth, DNA repair and differentiation, is an attractive target for development of useful anticancer drugs in tumors that are E2F oncogene addicted. A peptide, isolated from phage clones, based on its binding to an E2F-1 consensus sequence, was cytotoxic against a wide range of cancer cell lines. The peptide was coupled to penetratin (PEP) and tested against prostate cancer cell lines. As the PEP was found to be relatively unstable in serum, it was encapsulated in PEGylated liposomes for in vivo studies. The peptide was cytotoxic against prostate cell lines at low micromolar concentrations. Treatment of mice bearing the human Du-145 human prostate tumor with the PEP encapsulated in PEGylated liposomes (PL-PEP) caused tumor regression without significant toxicity. The liposome encapsulated PEP has promise as an antitumor agent, alone or in combination with inhibitors of DNA synthesis.
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