| Generation of ammodytoxin-anti-cathepsin B immuno-conjugate as a model for delivery of secretory phospholipase A2 into cancer cells. | |
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MedLine Citation:
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PMID: 18221975 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Ales Premzl; Lidija Kovacic; Beata Halassy; Igor Krizaj |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-12-14 |
Journal Detail:
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Title: Toxicon : official journal of the International Society on Toxinology Volume: 51 ISSN: 0041-0101 ISO Abbreviation: Toxicon Publication Date: 2008 Apr |
Date Detail:
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Created Date: 2008-03-17 Completed Date: 2008-08-28 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 1307333 Medline TA: Toxicon Country: England |
Other Details:
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Languages: eng Pagination: 754-64 Citation Subset: IM |
Affiliation:
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Department of Biochemistry, Molecular and Structural Biology, Jozef Stefan Institute, Jamova Street 39, SI-1000 Ljubljana, Slovenia. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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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