Document Detail


Generation of ammodytoxin-anti-cathepsin B immuno-conjugate as a model for delivery of secretory phospholipase A2 into cancer cells.
MedLine Citation:
PMID:  18221975     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Ammodytoxin C (AtxC) is a toxic secreted phospholipase A2 (sPLA2) from the venom of Vipera ammodytes snake. To evaluate its potential to kill cancer cells, the toxin was cross-linked to the monoclonal antibody against cathepsin B which endocytoses upon binding to cathepsin B, an antigen overexpressed on the plasma membrane of cancer cells. A photo-reactive derivative of AtxC, possessing the same biological activity as the native toxin, was reacted with antibodies to form a covalent immuno-conjugate. In conditions of the cytosolic redox potential, AtxC was gradually released from the conjugate due to reduction of the disulfide bond in the spacer arm of the cross-linker. The phospholipase activity of the preparation reached maximum in 10min and then decreased gradually. As demonstrated by fluorescence microscopy, the immuno-conjugate targeted Caco-2 colon adenocarcinoma cells but was very slowly internalized, the likely reason of only slight cytotoxicity being observed. Despite the lack of a clear cytotoxic effect of AtxC-antibody conjugate on Caco-2 cells, we demonstrated in this work a new methodology for the targeted delivery of (toxic) sPLA2 into cells, promising in research or therapy.
Authors:
Ales Premzl; Lidija Kovacic; Beata Halassy; Igor Krizaj
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-12-14
Journal Detail:
Title:  Toxicon : official journal of the International Society on Toxinology     Volume:  51     ISSN:  0041-0101     ISO Abbreviation:  Toxicon     Publication Date:  2008 Apr 
Date Detail:
Created Date:  2008-03-17     Completed Date:  2008-08-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1307333     Medline TA:  Toxicon     Country:  England    
Other Details:
Languages:  eng     Pagination:  754-64     Citation Subset:  IM    
Affiliation:
Department of Biochemistry, Molecular and Structural Biology, Jozef Stefan Institute, Jamova Street 39, SI-1000 Ljubljana, Slovenia.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Monoclonal / immunology*,  metabolism
Antineoplastic Agents / administration & dosage*,  therapeutic use
Caco-2 Cells
Cathepsin B / immunology*
Drug Delivery Systems
Group II Phospholipases A2 / immunology,  metabolism*
Humans
Immunoconjugates
Neoplasms / drug therapy
Phospholipases A2 / metabolism*
Viper Venoms / immunology,  metabolism*
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antineoplastic Agents; 0/Immunoconjugates; 0/Viper Venoms; EC 3.1.1.4/Group II Phospholipases A2; EC 3.1.1.4/Phospholipases A2; EC 3.1.1.4/ammodytoxin C; EC 3.4.22.1/Cathepsin B

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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