| Claudin-4-targeting of diphtheria toxin fragment A using a C-terminal fragment of Clostridium perfringens enterotoxin. | |
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MedLine Citation:
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PMID: 20226859 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Claudin (CL)-4, a tight junction protein, is overexpressed in some human neoplasias, including ovarian, breast, pancreatic and prostate cancers. The targeting of CL-4 is a novel strategy for tumor therapy. We previously found that the C-terminal fragment of Clostridium perfringens enterotoxin (C-CPE) binds to CL-4. In the present study, we genetically prepared a novel CL-4-targeting molecule (DTA-C-CPE) by fusion of C-CPE and diphtheria toxin fragment A (DTA). Although DTA is not toxic to CL-4-expressing L cells, even at 20 microg/ml, DTA-C-CPE is toxic to CL-4-expressing L cells at 1 microg/ml. DTA-C-CPE-induced cytotoxicity was attenuated by pretreatment of the cells with C-CPE but not bovine serum albumin, indicating that DTA-C-CPE may bind to CL-4-expressing L cells through its C-CPE domain. To evaluate the specificity of DTA-C-CPE, we examined its cytotoxic effects in L cells that express CL-1, -2, -4 or -5. We found that DTA-C-CPE was toxic to only CL-4-expressing L cells. Thus, C-CPE may be a promising ligand for the development of cancer-targeting systems. |
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Authors:
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Hideki Kakutani; Masuo Kondoh; Rie Saeki; Makiko Fujii; Yoshiteru Watanabe; Hiroyuki Mizuguchi; Kiyohito Yagi |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-03-11 |
Journal Detail:
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Title: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft für Pharmazeutische Verfahrenstechnik e.V Volume: 75 ISSN: 1873-3441 ISO Abbreviation: Eur J Pharm Biopharm Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-05-24 Completed Date: 2010-09-09 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9109778 Medline TA: Eur J Pharm Biopharm Country: Netherlands |
Other Details:
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Languages: eng Pagination: 213-7 Citation Subset: IM |
Copyright Information:
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Copyright 2010 Elsevier B.V. All rights reserved. |
Affiliation:
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Laboratory of Bio-Functional Molecular Chemistry, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antineoplastic Agents / administration & dosage, pharmacology Cattle Cell Line Diphtheria Toxin / administration & dosage*, chemistry, pharmacology Drug Delivery Systems* Enterotoxins / chemistry* Fibroblasts / drug effects, metabolism Ligands Membrane Proteins / metabolism* Mice Neoplasms / drug therapy, physiopathology Peptide Fragments / administration & dosage*, chemistry, pharmacology Protein Binding Serum Albumin, Bovine / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Diphtheria Toxin; 0/Enterotoxins; 0/Ligands; 0/Membrane Proteins; 0/Peptide Fragments; 0/Serum Albumin, Bovine; 0/claudin 4; 0/diphtheria toxin fragment A; 0/enterotoxin, Clostridium |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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