A novel peptide that inhibits E2F transcription and regresses prostate tumor xenografts

Autor: John E. Kerrigan, Nitu Bansal, Kathleen W. Scotto, Tazeem Shaik, Olga B. Garbuzenko, Debabrata Banerjee, Emine Ercikan Abali, Xiaoqi Xie, Tamara Minko, Joseph R. Bertino, Nadine Johnson-Farley
Rok vydání: 2014
Předmět:
Zdroj: Oncotarget
ISSN: 1949-2553
Popis: // Xiaoqi Xie 1 , Nitu Bansal 1 , Tazeem Shaik 1 , John E. Kerrigan 1 , Tamara Minko 2 , Olga Garbuzenko 2 ,Emine Ercikan Abali 3 , Nadine Johnson-Farley 1 , Debabrata Banerjee 1 , Kathleen W. Scotto 1 and Joseph R Bertino 1 1 Rutgers Cancer Institute of New Jersey 2 Department of Pharmaceutics Rutgers, the State University of New Jersey,Piscataway, New Jersey 3 Departments of Pharmacology, Biochemistry, and Medicine,Robert Wood Johnson Medical School, Rutgers,The State University of New Jersey, New Brunswick, NJ Correspondence: Joseph R Bertino, email: // Keywords : prostate cancer, penetratin-peptide, Du-145 cells. Received : February 11, 2014 Accepted : March 9, 2014 Published : March 11, 2014 Abstract 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.
Databáze: OpenAIRE