title: The effect of proteolysis on the induction of cell death by monomeric alpha-lactalbumin.
abstract: α-Lactalbumin (α-la) is a major whey protein found in milk. Previous data suggested that α-la has antiproliferative effects in human adenocarcinoma cell lines such as Caco-2 and HT-29. However, the cell death inducing α-la was not a naturally occurring monomer but either a multimeric variant or an α-la:oleic acid complex (HAMLET/BAMLET). Proteolysis showed that both human and bovine α-la are susceptible to digestion. ELISA assays assessing cell death with the native undigested α-la fractions showed that undigested protein fractions did have a significant cell death effect on CaCo-2 cells. Bovine α-la was also more effective than human α-la. A reduction in activity corresponded with lower concentrations of the protein and partial digestion and fragmentation of the protein using trypsin and pepsin. This suggests that the tertiary structure is vital for the apoptotic effect.
authors.affiliation: CAMBio, Letterkenny Institute of Technology, Port Road, Letterkenny, Co. Donegal, Ireland. Electronic address: wolfram.bruck@lyit.ie.
authors.forename: Wolfram M
authors.initials: WM
authors.lastname: Brück
authors.affiliation: Food Microbial Sciences Unit, School of Chemistry, Food and Pharmacy, University of Reading, Reading, UK.
authors.forename: Glenn R
authors.initials: GR
authors.lastname: Gibson
authors.affiliation: Technische Universität München (TUM), Department of Chemistry, Division of Industrial Biocatalysis, Lichtenberg Str. 4, 85748 Garching bei München, Germany.
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Brück
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D018938:Caco-2 Cells; D002417:Cattle; D016923:Cell Death / Q000187:drug effects; D006801:Humans; D007768:Lactalbumin / Q000737:chemistry* / Q000494:pharmacology; D019301:Oleic Acid / Q000737:chemistry*; D010434:Pepsin A / Q000737:chemistry; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D059748:Proteolysis; D021241:Spectrometry, Mass, Electrospray Ionization; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014357:Trypsin / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D019301:Oleic Acid; D007768:Lactalbumin; D014357:Trypsin; D010434:Pepsin A
keywords: Cell death; Pepsin; Proteolysis; Trypsin; alpha-Lactalbumin