title: Necrosis-inducing peptide has the beneficial effect on killing tumor cells through neuropilin (NRP-1) targeting.
abstract: The therapeutic efficacy of most anti-cancer drugs depends on their apoptosis-inducing 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.
authors.affiliation: Department of Biochemistry, Chosun University School of Medicine, Dong-Gu, Gwang-Ju, Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, Chosun University School of Medicine, Dong-Gu, Gwang-Ju, Korea.
authors.forename: Ji-Hae
authors.initials: JH
authors.lastname: Han
authors.affiliation: Department of Laboratory Medicine, Chosun University School of Medicine, Dong-Gu, Gwang-Ju, Korea.
authors.forename: Geon
authors.initials: G
authors.lastname: Park
authors.affiliation: Korea Basic Science Institute Gwang-Ju Center, Chonnam National University, Buk-Gu, Gwang-Ju, Korea.
authors.forename: Young-Woo
authors.initials: YW
authors.lastname: Seo
authors.affiliation: School of Life Science and Biotechnology, Korea University, Seoul, Korea.
authors.forename: Cheol-Won
authors.initials: CW
authors.lastname: Yun
authors.affiliation: Genoflux. Co., Ltd., Sejong City, Korea.
authors.forename: Byung-Chul
authors.initials: BC
authors.lastname: Lee
authors.affiliation: School of Pharmacy, Chung-Ang University, Dongjak-Gu, Seoul, Korea.
authors.forename: Jeehyeon
authors.initials: J
authors.lastname: Bae
authors.affiliation: Department of Biochemistry, Chosun University School of Medicine, Dong-Gu, Gwang-Ju, Korea.
authors.forename: Ae Ran
authors.initials: AR
authors.lastname: Moon
authors.affiliation: Department of Biochemistry, Chosun University School of Medicine, Dong-Gu, Gwang-Ju, Korea.
authors.forename: Tae-Hyoung
authors.initials: TH
authors.lastname: Kim
mesh_terms: D000818:Animals; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D058990:Molecular Targeted Therapy; D009336:Necrosis; D039942:Neuropilin-1 / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D000072417:Protein Domains; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: C498702:PMAIP1 protein, human; D010446:Peptide Fragments; D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins; D039942:Neuropilin-1
keywords: NRP-1; Noxa; mitochondrial targeting domain; necrosis; pro-necrotic peptide