The targeted proteins in tumor cells treated with the α-lactalbumin-oleic acid complex examined by descriptive and quantitative liquid chromatography-tandem mass spectrometry.

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.