Journal
FEBS LETTERS
Volume 592, Issue 1, Pages 103-111Publisher
WILEY
DOI: 10.1002/1873-3468.12922
Keywords
anticancer peptide; ErbB2; MTD; necrosis
Funding
- Ministry of Health and Welfare of the Korean government [HI14C2025]
- Ministry of Science, ICT, and Future Planning [NRF-2014R1A2A1A11050442]
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Many anticancer drugs target epidermal growth factor receptors to inhibit receptor tyrosine kinases and tumor growth. Here, we show that an ErbB2-targeting pronecrotic peptide (KWSY:MTD) selectively kills tumor cells expressing ErbB2 in vitro. An antibody against ErbB2 inhibits KWSY:MTD-induced cell death. KWSY:MTD causes membrane permeability which allows propidium iodide entry into the cytosol and the release of HMGB1 into the media, indicative of necrosis. Mitochondrial swelling occurs in response to KWSY:MTD. Moreover, in vivo analysis using a mouse model shows that KWSY:MTD partially suppressed growth in tumor tissue bearing ErbB2-expressing cells, but did not have obvious toxicity in mouse liver or kidney tissue. Taken together, KWSY:MTD has potential as an ErbB2-targeting anticancer drug.
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