EGFR-targeting, β-defensin-tailored fusion protein exhibits high therapeutic efficacy against EGFR-expressed human carcinoma via mitochondria-mediated apoptosis

Acta Pharmacologica Sinica
Wen-Juan LiuYong-Su Zhen

Abstract

Defensins play an essential role in innate immunity. In this study, a novel recombinant β-defensin that targets the epidermal growth factor receptor (EGFR) was designed and prepared. The EGFR-targeting β-defensin consists of an EGF-derived oligopeptide (Ec), a β-defensin-1 peptide (hBD1) and a lidamycin-derived apoprotein (LDP), which serves as the "scaffold" for the fusion protein (Ec-LDP-hBD1). Ec-LDP-hBD1 effectively bound to EGFR highly expressed human epidermoid carcinoma A431 cells. The cytotoxicity of Ec-LDP-hBD1 to EGFR highly expressed A431 cells was more potent than that to EGFR low-expressed human lung carcinoma A549 and H460 cells (the IC50 values in A431, A549, and H460 cells were 1.8 ± 0.55, 11.9 ± 0.51, and 5.19 ± 1.21 μmol/L, respectively); in addition, the cytotoxicity of Ec-LDP-hBD1 was much stronger than that of Ec-LDP and hBD1. Moreover, Ec-LDP-hBD1 suppressed cancer cell proliferation and induced mitochondria-mediated apoptosis. Its in vivo anticancer action was evaluated in athymic mice with A431 and H460 xenografts. The mice were administered Ec-LDP-hBD1 (5, 10 mg/kg, i.v.) two times with a weekly interval. Administration of Ec-LDP-hBD1 markedly inhibited the tumor growth without significant body weight c...Continue Reading

References

May 4, 2005·Cellular and Molecular Life Sciences : CMLS·N Papo, Y Shai
Feb 22, 2008·Anti-cancer Agents in Medicinal Chemistry·Rong-guang Shao, Yong-su Zhen
Mar 1, 2008·International Immunology·Isao NagaokaMichimasa Hirata
Feb 3, 2009·Journal of Proteomics·Nathalie DroinEric Solary
Aug 19, 2011·The FEBS Journal·Andreas CederlundBirgitta Agerberth
Aug 23, 2012·Frontiers in Immunology·Hannah UlmHans-Georg Sahl
Sep 18, 2012·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Qin RuYong-Su Zhen
Mar 7, 2013·Mucosal Immunology·C J KellyS P Colgan
Jun 13, 2013·Human Immunology·Justyna JarczakEmilia Bagnicka
Jan 13, 2015·Cytokine & Growth Factor Reviews·Meggy Suarez-CarmonaMichael Herfs
Jan 19, 2016·Advanced Drug Delivery Reviews·Ru WenShanta Dhar
Sep 1, 2016·Annual Review of Cell and Developmental Biology·Kay O SchinkHarald Stenmark
Dec 4, 2016·Methods in Molecular Biology·Wenxun GanRuth Nussinov
Apr 11, 2017·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Jian XuYong-Su Zhen
Feb 13, 2018·Oncotarget·Ya-Wen SunWen-Juan Liu

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Citations

Sep 13, 2018·Laboratory Investigation; a Journal of Technical Methods and Pathology·Wen-Juan LiuHui Zhu
Mar 23, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Kanyani SangpheakThanyada Rungrotmongkol
Oct 30, 2020·International Journal of Molecular Sciences·Lanfeng DongJiri Neuzil
May 1, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Thitinan AiebchunThanyada Rungrotmongkol
May 29, 2021·RSC Medicinal Chemistry·Kamonpan SanachaiThanyada Rungrotmongkol

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Methods Mentioned

BETA
PCR
ELISA
fluorescence-activated
saturation binding
fluorescence imaging
xenograft
xenografts
Flow cytometry
Flow
transmission electron microscopy

Software Mentioned

SPSS
GraphPad Prism
Prism
GraphPad

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