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

Authors
Kim, Ji-YoungHan, Ji-HaePark, GeonSeo, Young-WooYun, Cheol-WonLee, Byung-ChulBae, JeehyeonMoon, Ae RanKim, Tae-Hyoung
Issue Date
31-5월-2016
Publisher
IMPACT JOURNALS LLC
Keywords
necrosis; pro-necrotic peptide; mitochondrial targeting domain; NRP-1; noxa
Citation
ONCOTARGET, v.7, no.22, pp.32449 - 32461
Indexed
SCIE
SCOPUS
Journal Title
ONCOTARGET
Volume
7
Number
22
Start Page
32449
End Page
32461
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/88613
DOI
10.18632/oncotarget.8719
ISSN
1949-2553
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.
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생명과학대학 (생명과학부)
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