Document Detail


Oleic acid is a key cytotoxic component of HAMLET-like complexes.
MedLine Citation:
PMID:  22628302     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
HAMLET is a complex of α-lactalbumin (α-LA) with oleic acid (OA) that selectively kills tumor cells and Streptococcus pneumoniae. To assess the contribution of the proteinaceous component to cytotoxicity of HAMLET, OA complexes with proteins structurally and functionally distinct from α-LA were prepared. Similar to HAMLET, the OA complexes with bovine β-lactoglobulin (bLG) and pike parvalbumin (pPA) (bLG-OA-45 and pPA-OA-45, respectively) induced S. pneumoniae D39 cell death. The activation mechanisms of S. pneumoniae death for these complexes were analogous to those for HAMLET, and the cytotoxicity of the complexes increased with OA content in the preparations. The half-maximal inhibitory concentration for HEp-2 cells linearly decreased with rise in OA content in the preparations, and OA concentration in the preparations causing HEp-2 cell death was close to the cytotoxicity of OA alone. Hence, the cytotoxic action of these complexes against HEp-2 cells is induced mostly by OA. Thermal stabilization of bLG upon association with OA implies that cytotoxicity of bLG-OA-45 complex cannot be ascribed to molten globule-like conformation of the protein component. Overall, the proteinaceous component of HAMLET-like complexes studied is not a prerequisite for their activity; the cytotoxicity of these complexes is mostly due to the action of OA.
Authors:
Sergei E Permyakov; Ekaterina L Knyazeva; Leysan M Khasanova; Roman S Fadeev; Andrei P Zhadan; Hazeline Roche-Hakansson; Anders P Håkansson; Vladimir S Akatov; Eugene A Permyakov
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biological chemistry     Volume:  393     ISSN:  1437-4315     ISO Abbreviation:  Biol. Chem.     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-05-25     Completed Date:  2013-02-14     Revised Date:  2014-05-12    
Medline Journal Info:
Nlm Unique ID:  9700112     Medline TA:  Biol Chem     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  85-92     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Anti-Bacterial Agents / chemistry,  pharmacology*
Antineoplastic Agents / chemistry,  pharmacology*
Cattle
Cell Death / drug effects
Cell Line, Tumor
Cell Survival / drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Humans
Lactalbumin / chemistry*,  pharmacology*,  toxicity
Lactoglobulins / chemistry
Microbial Sensitivity Tests
Oleic Acid / chemistry,  pharmacology*,  toxicity
Parvalbumins / chemistry
Protein Stability
Streptococcus pneumoniae / cytology,  drug effects*
Structure-Activity Relationship
Temperature
Chemical
Reg. No./Substance:
0/Anti-Bacterial Agents; 0/Antineoplastic Agents; 0/Lactoglobulins; 0/Parvalbumins; 2UMI9U37CP/Oleic Acid; 9013-90-5/Lactalbumin

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


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