title: Oleic acid is a key cytotoxic component of HAMLET-like complexes.
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.
authors.affiliation: Institute for Biological Instrumentation, Russian Academy of Sciences, Pushchino, Moscow 142290, Russia. permyakov.s@gmail.com
authors.forename: Sergei E
authors.initials: SE
authors.lastname: Permyakov
authors.forename: Ekaterina L
authors.initials: EL
authors.lastname: Knyazeva
authors.forename: Leysan M
authors.initials: LM
authors.lastname: Khasanova
authors.forename: Roman S
authors.initials: RS
authors.lastname: Fadeev
authors.forename: Andrei P
authors.initials: AP
authors.lastname: Zhadan
authors.forename: Hazeline
authors.initials: H
authors.lastname: Roche-Hakansson
authors.forename: Anders P
authors.initials: AP
authors.lastname: Håkansson
authors.forename: Vladimir S
authors.initials: VS
authors.lastname: Akatov
authors.forename: Eugene A
authors.initials: EA
authors.lastname: Permyakov
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002417:Cattle; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007768:Lactalbumin / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D007782:Lactoglobulins / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D019301:Oleic Acid / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D010320:Parvalbumins / Q000737:chemistry; D055550:Protein Stability; D013296:Streptococcus pneumoniae / Q000166:cytology / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013696:Temperature
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D007782:Lactoglobulins; D010320:Parvalbumins; D019301:Oleic Acid; D007768:Lactalbumin