title: Heat-treatment method for producing fatty acid-bound alpha-lactalbumin that induces tumor cell death.
abstract: HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells), which was identified in human breast milk as an alpha-lactalbumin (LA)-oleic acid complex, kills tumor cells, selectively. Although it may have potential as a therapeutic agent against various tumor cells, only low-volume methods for its production exist. In this study, heat treatment was used to produce complexes from LAs and oleic acid using a simple method. In the case of human LA and oleic acid, heat-treated samples apparently showed much stronger activities than those treated at room temperature, with cytotoxicities equal to that of HAMLET. Furthermore, circular dichroism spectroscopy revealed that heat-treated samples lost their tertiary structure, suggesting a molten globule as oleic acid-bound LA. BLA samples also showed strong activities by heat treatment. Batch production with heat treatment can efficiently convert LAs into tumoricidal complexes.
authors.affiliation: Division of Life Science, Graduate School of Life Science, Hokkaido University, Kita 10 Nishi 8, Kitaku, Sapporo, Hokkaido 060-0810, Japan.
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Kamijima
authors.forename: Ayaka
authors.initials: A
authors.lastname: Ohmura
authors.forename: Toshiya
authors.initials: T
authors.lastname: Sato
authors.forename: Kaoru
authors.initials: K
authors.lastname: Akimoto
authors.forename: Miki
authors.initials: M
authors.lastname: Itabashi
authors.forename: Mineyuki
authors.initials: M
authors.lastname: Mizuguchi
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Kamiya
authors.forename: Takashi
authors.initials: T
authors.lastname: Kikukawa
authors.forename: Tomoyasu
authors.initials: T
authors.lastname: Aizawa
authors.forename: Masayuki
authors.initials: M
authors.lastname: Takahashi
authors.forename: Keiichi
authors.initials: K
authors.lastname: Kawano
authors.forename: Makoto
authors.initials: M
authors.lastname: Demura
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D017209:Apoptosis; D002417:Cattle; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006358:Hot Temperature; D006801:Humans; D007768:Lactalbumin / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D009369:Neoplasms / Q000378:metabolism*; D019301:Oleic Acid / Q000737:chemistry; D009829:Oleic Acids / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; C506422:HAMLET complex, human; D009829:Oleic Acids; D019301:Oleic Acid; D007768:Lactalbumin