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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Turk, Boris / Wittinghofer, Alfred


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

1, 2 / 1 / Leysan M. Khasanova1, 2 / Roman S. Fadeev3 / Andrei P. Zhadan1 / Hazeline Roche-Hakansson4 / Anders P. Håkansson4, 5 / Vladimir S. Akatov3 / Eugene A. Permyakov1, 2

1Institute for Biological Instrumentation, Russian Academy of Sciences, Pushchino, Moscow 142290, Russia

2Department of Biomedical Engineering, Pushchino State University, Pushchino, Moscow 142290, Russia

3Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Moscow 142290, Russia

4Department of Microbiology and Immunology, University at Buffalo, Buffalo, NY 14214, USA

5Witebsky Center for Microbial Pathogenesis and Immunology, University at Buffalo, Buffalo, NY 14214, USA

Corresponding authors

Citation Information: . Volume 393, Issue 1-2, Pages 85–92, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: 10.1515/BC-2011-230, January 2012

Publication History

Received:
2011-10-13
Accepted:
2011-11-24

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 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.

Keywords: α-lactalbumin; β-lactoglobulin; cytotoxicity; HAMLET; oleic acid; parvalbumin

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