Oncotarget

Research Papers:

This article has been corrected. Correction in: Oncotarget. 2018; 9:26977.

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

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

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2016; 7:32449-32461. https://doi.org/10.18632/oncotarget.8719

Metrics: PDF 2015 views  |   HTML 2177 views  |   ?  


Abstract

Ji-Young Kim1,*, Ji-Hae Han1,*, Geon Park2, Young-Woo Seo3, Cheol-Won Yun4, Byung-Chul Lee5, Jeehyeon Bae6, Ae Ran Moon1,*, Tae-Hyoung Kim1,*

1Department of Biochemistry, Chosun University School of Medicine, Dong-Gu, Gwang-Ju, Korea

2Department of Laboratory Medicine, Chosun University School of Medicine, Dong-Gu, Gwang-Ju, Korea

3Korea Basic Science Institute Gwang-Ju Center, Chonnam National University, Buk-Gu, Gwang-Ju, Korea

4School of Life Science and Biotechnology, Korea University, Seoul, Korea

5Genoflux. Co., Ltd., Sejong City, Korea

6School of Pharmacy, Chung-Ang University, Dongjak-Gu, Seoul, Korea

*These authors equally contributed to this work

Correspondence to:

Tae-Hyoung Kim, email: thkim65@chosun.ac.kr

Ae Ran Moon, email: aeranmoon2009@gmail.com

Keywords: necrosis, pro-necrotic peptide, mitochondrial targeting domain, NRP-1, Noxa

Received: November 05, 2015     Accepted: March 28, 2016     Published: April 13, 2016

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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 8719