Document Detail

Claudin-4-targeting of diphtheria toxin fragment A using a C-terminal fragment of Clostridium perfringens enterotoxin.
MedLine Citation:
PMID:  20226859     Owner:  NLM     Status:  MEDLINE    
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.
Hideki Kakutani; Masuo Kondoh; Rie Saeki; Makiko Fujii; Yoshiteru Watanabe; Hiroyuki Mizuguchi; Kiyohito Yagi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-03-11
Journal Detail:
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:
Created Date:  2010-05-24     Completed Date:  2010-09-09     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9109778     Medline TA:  Eur J Pharm Biopharm     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  213-7     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier B.V. All rights reserved.
Laboratory of Bio-Functional Molecular Chemistry, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
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MeSH Terms
Antineoplastic Agents / administration & dosage,  pharmacology
Cell Line
Diphtheria Toxin / administration & dosage*,  chemistry,  pharmacology
Drug Delivery Systems*
Enterotoxins / chemistry*
Fibroblasts / drug effects,  metabolism
Membrane Proteins / metabolism*
Neoplasms / drug therapy,  physiopathology
Peptide Fragments / administration & dosage*,  chemistry,  pharmacology
Protein Binding
Serum Albumin, Bovine / pharmacology
Reg. No./Substance:
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

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