Antitumor and modeling studies of a penetratin-peptide that targets E2F-1 in small cell lung cancer

Xiaoqi Xie, John E. Kerrigan, Tamara Minko, Olga Garbuzenko, Kuo Chieh Lee, Alex Scarborough, Emine Ercikan Abali, Tulin Budak-Alpdogan, Nadine Johnson-Farley, Debabrata Banerjee, Kathleen W. Scotto, Joseph R. Bertino

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


E2F-1, a key transcription factor necessary for cell growth, DNA repair, and differentiation, is an attractive target for development of anticancer drugs in tumors that are E2F "oncogene addicted". We identified a peptide isolated from phage clones that bound tightly to the E2F-1 promoter consensus sequence. The peptide was coupled to penetratin to enhance cellular uptake. Modeling of the penetratin-peptide (PEP ) binding to the DNA E2F-1 promoter demonstrated favorable interactions that also involved the participation of most of the penetratin sequence. The penetratin-peptide (PEP ) demonstrated potent in vitro cytotoxic effects against a range of cancer cell lines, particularly against Burkitt lymphoma cells and small cell lung cancer (SCLC) cells. Further studies in the H-69 SCLC cell line showed that the PEP inhibited transcription of E2F-1 and also several important E2F-regulated enzymes involved in DNA synthesis, namely, thymidylate synthase, thymidine kinase, and ribonucleotide reductase. As the PEP was found to be relatively unstable in serum, it was encapsulated in PE Gylated liposomes (PL-PEP ) for in vivo studies. Treatment of mice bearing the human small cell lung carcinoma H-69 with the PEP encapsulated in PE Gylated liposomes 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.

Original languageEnglish (US)
Pages (from-to)742-751
Number of pages10
JournalCancer Biology and Therapy
Issue number8
StatePublished - Aug 2013

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research


  • E2F-1
  • Mouse xenografts
  • Pegylated liposomes
  • Penetratin peptide
  • Small cell lung cancer


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