Premium
Designing a cancer therapeutic peptide by combining the mitochondrial targeting domain of Noxa and ErbB2‐targeting moieties
Author(s) -
Han JiHye,
Park Junghee,
Seo YoungWoo,
Kim TaeHyoung
Publication year - 2018
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12922
Subject(s) - propidium iodide , cancer research , tyrosine kinase , in vivo , epidermal growth factor receptor , programmed cell death , cancer cell , apoptosis , receptor , receptor tyrosine kinase , biology , chemistry , microbiology and biotechnology , kinase , cancer , biochemistry , genetics
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 HMGB 1 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.