Fang B, Zhang M, Fan X, Ren F Z
Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing, 100083, China.
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.
J Dairy Sci. 2016 Aug;99(8):5991-6004. doi: 10.3168/jds.2016-10971. Epub 2016 May 26.
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.
α-乳白蛋白-油酸（α-LA-OA）复合物在动物模型和临床试验中已表现出选择性抗肿瘤活性。尽管细胞凋亡和自噬被激活，并且几种细胞器的功能响应α-LA-OA而受到破坏，但详细的抗肿瘤机制仍不清楚。在本研究中，我们使用了一种新技术，即相对和绝对定量的等压标记，来分析用α-LA-OA处理的肿瘤细胞的蛋白质组。我们鉴定出112种差异表达蛋白：95种上调以满足肿瘤细胞的代谢；17种下调且是α-LA-OA的作用靶点。根据差异表达蛋白，α-LA-OA通过破坏细胞骨架稳定性和细胞运动性，并通过抑制DNA、脂质和ATP合成，导致细胞应激和程序性细胞死亡的激活，从而发挥其抗肿瘤活性。本研究提供了对α-LA-OA抗肿瘤活性的系统评估，确定了其相互作用靶点，并建立了α-LA-OA用于癌症治疗的理论基础。
