title: The targeted proteins in tumor cells treated with the α-lactalbumin-oleic acid complex examined by descriptive and quantitative liquid chromatography-tandem mass spectrometry.
abstract: An α-lactalbumin-oleic acid (α-LA-OA) complex has exhibited selective antitumor activity in animal models and clinical trials. Although apoptosis and autophagy are activated and the functions of several organelles are disrupted in response to α-LA-OA, the detailed antitumor mechanism remains unclear. In this study, we used a novel technique, isobaric tags for relative and absolute quantitation, to analyze the proteome of tumor cells treated with α-LA-OA. We identified 112 differentially expressed proteins: 95 were upregulated to satisfy the metabolism of tumor cells; 17 were downregulated and targets of α-LA-OA. According to the differentially expressed proteins, α-LA-OA exerted its antitumor activity by disrupting cytoskeleton stability and cell motility, and by inhibiting DNA, lipid, and ATP synthesis, leading to cellular stress and activation of programmed cell death. This study provides a systematic evaluation of the antitumor activity of α-LA-OA, identifying its interacting targets and establishing the theoretical basis of α-LA-OA for use in cancer therapy.
authors.affiliation: Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing, 100083, China. Electronic address: 49631263@qq.com.
authors.forename: B
authors.initials: B
authors.lastname: Fang
authors.affiliation: Key Laboratory of Functional Dairy, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 100083, China; School of Food Science and Chemical Engineering, Beijing Technology and Business University, Beijing, 100048, China.
authors.forename: M
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Beijing Laboratory for Food Quality and Safety, China Agricultural University, Beijing, 100083, China.
authors.forename: X
authors.initials: X
authors.lastname: Fan
authors.affiliation: Key Laboratory of Functional Dairy, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 100083, China; Beijing Laboratory for Food Quality and Safety, China Agricultural University, Beijing, 100083, China.
authors.forename: F Z
authors.initials: FZ
authors.lastname: Ren
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D002853:Chromatography, Liquid; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D007768:Lactalbumin / Q000494:pharmacology*; D019301:Oleic Acid / Q000494:pharmacology*; D020543:Proteome; D053719:Tandem Mass Spectrometry
chemical_list: D000970:Antineoplastic Agents; D020543:Proteome; D019301:Oleic Acid; D007768:Lactalbumin
keywords: antitumor; human alpha-lactalbumin made lethal to tumor cells (HAMLET); isobaric tag for relative and absolute quantitation (iTRAQ); proteomics