Necrosis-inducing peptide has the beneficial effect on killing tumor cells through neuropilin (NRP-1) targeting
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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
Tae-Hyoung Kim, email: [email protected]
Ae Ran Moon, email: [email protected]
Keywords: necrosis, pro-necrotic peptide, mitochondrial targeting domain, NRP-1, Noxa
Received: November 05, 2015 Accepted: March 28, 2016 Published: April 13, 2016
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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