Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei 11031, Taiwan.
School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan.
Molecules. 2022 Jul 15;27(14):4533. doi: 10.3390/molecules27144533.
(MO), known as lemon balm, is a popular ingredient blended in herbal tea. In recent decades, the bioactivities of MO have been studied in sub-health and pathological status, highlighting MO possesses multiple pharmacological effects. We previously showed that hot water MO extract exhibited anticancer activity in colorectal cancer (CRC). However, the detailed mechanisms underlying MO-induced cell death remain elusive. To elucidate the anticancer regulation of MO extract in colon cancer, a data-driven analysis by proteomics approaches and bioinformatics analysis was applied. An isobaric tandem mass tags-based quantitative proteome analysis using liquid chromatography-coupled tandem mass spectrometry was performed to acquire proteome-wide expression data. The over-representation analysis and functional class scoring method were implemented to interpret the MO-induced biological regulations. In total, 3465 quantifiable proteoforms were identified from 24,348 peptides, with 67 upregulated and 54 downregulated proteins in the MO-treated group. Mechanistically, MO impeded mitochondrial respiratory electron transport by triggering a reactive oxygen species (ROS)-mediated oxidative stress response. MO hindered the mitochondrial membrane potential by reducing the protein expression in the electron transport chain, specifically the complex I and II, which could be restored by ROS scavenger. The findings comprehensively elucidate how MO hot water extract activates antitumor effects in colorectal cancer (CRC) cells.
（MO），也被称为柠檬香脂，是一种常用于草本茶的流行成分。近几十年来，人们对 MO 在亚健康和病理状态下的生物活性进行了研究，强调 MO 具有多种药理作用。我们之前已经表明，热水 MO 提取物在结直肠癌（CRC）中具有抗癌活性。然而，MO 诱导细胞死亡的详细机制仍不清楚。为了阐明 MO 提取物对结肠癌的抗癌调节作用，我们应用了基于蛋白质组学方法和生物信息学分析的数据分析。使用液相色谱-串联质谱联用技术进行了基于等重串联质量标签的定量蛋白质组分析，以获取全蛋白质组表达数据。实施了过表达分析和功能分类评分方法来解释 MO 诱导的生物学调节。总共从 24348 个肽中鉴定出 3465 种可定量的蛋白质，其中 MO 处理组有 67 种上调蛋白和 54 种下调蛋白。从机制上讲，MO 通过触发活性氧（ROS）介导的氧化应激反应来阻碍线粒体呼吸电子传递。MO 通过降低电子传递链中的蛋白质表达来阻碍线粒体膜电位，特别是复合物 I 和 II，ROS 清除剂可以恢复这种表达。这些发现全面阐明了热水 MO 提取物如何在结直肠癌（CRC）细胞中激活抗肿瘤作用。
