title: The heparin-binding domain of HB-EGF as an efficient cell-penetrating peptide for drug delivery.
abstract: Cell-penetrating peptides (CPPs) have been shown to be potential drug carriers for cancer therapy. The inherently low immunogenicity and cytotoxicity of human-derived CPPs make them more suitable for intracellular drug delivery compared to other delivery vehicles. In this work, the protein transduction ability of a novel CPP (termed HBP) derived from the heparin-binding domain of HB-EGF was evaluated. Our data shows, for the first time, that HBP possesses similar properties to typical CPPs and is a potent drug delivery vector for improving the antitumor activity of impermeable MAP30. The intrinsic bioactivities of recombinant MAP30-HBP were well preserved compared to those of free MAP30. Furthermore, HBP conjugated to the C-terminus of MAP30 promoted the cellular uptake of recombinant MAP30-HBP. Moreover, the fusion of HBP to MAP30 gave rise to significantly enhanced cytotoxic effects in all of the tumor cell lines tested. In HeLa cells, this cytotoxicity was mainly caused by the induction of cell apoptosis. Further investigation revealed that HBP enhanced MAP30-induced apoptosis through the activation of the mitochondrial- and death receptor-mediated signaling pathways. In addition, the MAP30-HBP fusion protein caused more HeLa cells to become arrested in S phase compared to MAP30 alone. These results highlight the MAP30-HBP fusion protein as a promising drug candidate for cancer therapy and demonstrate HBP, a novel CPP derived from human HB-EGF, as a new potential vector for antitumor drug delivery. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China.
authors.forename: Xue-Wei
authors.initials: XW
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Li
authors.affiliation: Zhejiang Reachall Pharmaceutical Co. Ltd., Zhejiang, China.
authors.forename: Miao-Dan
authors.initials: MD
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China.
authors.forename: Xu-Zhong
authors.initials: XZ
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Zhejiang Reachall Pharmaceutical Co. Ltd., Zhejiang, China.|Shanghai University of Chinese Traditional Medicine, Shanghai, China.
authors.forename: Fu-Jun
authors.initials: FJ
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D057846:Cell-Penetrating Peptides / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D003001:Cloning, Molecular; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006367:HeLa Cells; D006493:Heparin / Q000737:chemistry / Q000378:metabolism; D066257:Heparin-binding EGF-like Growth Factor / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D029777:Momordica charantia / Q000737:chemistry; D011485:Protein Binding; D000072417:Protein Domains; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D054790:Ribosome Inactivating Proteins, Type 2 / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D016196:S Phase / Q000187:drug effects; D015398:Signal Transduction
chemical_list: D057846:Cell-Penetrating Peptides; D004337:Drug Carriers; D066257:Heparin-binding EGF-like Growth Factor; C066347:MAP30 protein, Momordica charantia; D011993:Recombinant Fusion Proteins; D054790:Ribosome Inactivating Proteins, Type 2; D006493:Heparin
keywords: antitumor activity; cell-penetrating peptide; drug delivery; hb-egf; heparin binding domain; map30