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Designing a cancer therapeutic peptide by combining the mitochondrial targeting domain of Noxa and ErbB2-targeting moieties.

FEBS Lett.. 2018-01; 
HanJi-Hye,ParkJunghee,SeoYoung-Woo,KimTae-Hy
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Peptide Synthesis … Materials and methods. Peptide synthesis. All synthesized peptides were purchased from GenScript (Piscataway, NJ, USA) or A&PEP (Chungbuk, Korea). All peptides were purified by rapid reverse phase-HPLC to homogeneity (ie, > 90%) and evaluated by mass spectrometry … Get A Quote

摘要

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 o... More

关键词

MTD ,ErbB2,anticancer peptide,necr