Necrosis-inducing peptide has the beneficial effect on killing tumor cells through neuropilin (NRP-1) targeting

Ji Ji Young Kim, Ji Hae Han, Geon Park, Young Woo Seo, Cheol-Won Yun, Byung Chul Lee, Jeehyeon Bae, Ae Ran Moon, Tae Hyoung Kim

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The therapeutic efficacy of most anti-cancer drugs depends on their apoptosisinducing abilities. Previously, we showed that a peptide containing the mitochondrial targeting domain (MTD) found in Noxa, a BH-3 only protein of Bcl-2 family, induces necrosis. Here, a fusion peptide of neuropilin-1 (NRP-1) targeting peptide and MTD peptide, designated tumor homing motif 17:MTD (TU17:MTD), was found to induce necrosis in cancer cells in vitro and to cause the regression of tumors when intravenously injected into mice bearing subcutaneous CT26 colorectal carcinoma tumors. The necrosis within tumor tissues was evident upon administering TU17:MTD. TU17:MTD penetrated into tumor cells by targeting to Neuropilin-1, which could be blocked by anti-NRP-1 antibody. The efficacy of TU17:MTD on tumor regression was higher than that of TU17:D(KLAKLAK)2, a fusion peptide of NRP-1 targeting peptide and a pro-apoptotic peptide. The necrotic cell death within tumor tissues was evident at day 1 after administering TU17:MTD systemically. Transplanted subcutaneous substantially reduced in size within two weeks and 5 days, respectively, with no apparent side effects. Together, these results propose that the pro-necrotic peptide MTD may present an alternative approach for development of targeted anti-cancer agents.

Original languageEnglish
Pages (from-to)32449-32461
Number of pages13
JournalOncotarget
Volume7
Issue number22
DOIs
Publication statusPublished - 2016 May 31

Keywords

  • Mitochondrial targeting domain
  • Necrosis
  • Noxa
  • NRP-1
  • Pro-necrotic peptide

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Kim, J. J. Y., Han, J. H., Park, G., Seo, Y. W., Yun, C-W., Lee, B. C., Bae, J., Moon, A. R., & Kim, T. H. (2016). Necrosis-inducing peptide has the beneficial effect on killing tumor cells through neuropilin (NRP-1) targeting. Oncotarget, 7(22), 32449-32461. https://doi.org/10.18632/oncotarget.8719