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Oleic acid is a key cytotoxic component of HAMLET-like complexes

Permyakov, Sergei E; Knyazeva, Ekaterina L; Khasanova, Leysan M; Fadeev, Roman S; Zhadan, Andrei P; Roche-Hakansson, Hazeline; Håkansson, Anders P LU ; Akatov, Vladimir S and Permyakov, Eugene A (2012) In Biological Chemistry 393(1-2). p.85-92
Abstract

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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Animals, Anti-Bacterial Agents, Antineoplastic Agents, Cattle, Cell Death, Cell Line, Tumor, Cell Survival, Dose-Response Relationship, Drug, Drug Screening Assays, Antitumor, Humans, Lactalbumin, Lactoglobulins, Microbial Sensitivity Tests, Oleic Acid, Parvalbumins, Protein Stability, Streptococcus pneumoniae, Structure-Activity Relationship, Temperature
in
Biological Chemistry
volume
393
issue
1-2
pages
8 pages
publisher
De Gruyter
external identifiers
  • Scopus:84856173469
ISSN
1437-4315
DOI
10.1515/BC-2011-230
language
English
LU publication?
yes
id
d8f0bd7e-ec75-4e3c-b891-e8653b023294
date added to LUP
2016-05-21 10:50:20
date last changed
2016-12-04 04:51:48
@misc{d8f0bd7e-ec75-4e3c-b891-e8653b023294,
  abstract     = {<p>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.</p>},
  author       = {Permyakov, Sergei E and Knyazeva, Ekaterina L and Khasanova, Leysan M and Fadeev, Roman S and Zhadan, Andrei P and Roche-Hakansson, Hazeline and Håkansson, Anders P and Akatov, Vladimir S and Permyakov, Eugene A},
  issn         = {1437-4315},
  keyword      = {Animals,Anti-Bacterial Agents,Antineoplastic Agents,Cattle,Cell Death,Cell Line, Tumor,Cell Survival,Dose-Response Relationship, Drug,Drug Screening Assays, Antitumor,Humans,Lactalbumin,Lactoglobulins,Microbial Sensitivity Tests,Oleic Acid,Parvalbumins,Protein Stability,Streptococcus pneumoniae,Structure-Activity Relationship,Temperature},
  language     = {eng},
  number       = {1-2},
  pages        = {85--92},
  publisher    = {ARRAY(0xb8c8428)},
  series       = {Biological Chemistry},
  title        = {Oleic acid is a key cytotoxic component of HAMLET-like complexes},
  url          = {http://dx.doi.org/10.1515/BC-2011-230},
  volume       = {393},
  year         = {2012},
}