Designing a cancer therapeutic peptide by combining the mitochondrial targeting domain of Noxa and ErbB2‐targeting moieties
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...
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Published in | FEBS letters Vol. 592; no. 1; pp. 103 - 111 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
England
01.01.2018
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Subjects | |
Online Access | Get full text |
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Summary: | 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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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0014-5793 1873-3468 |
DOI: | 10.1002/1873-3468.12922 |