Departamento de Biología Celular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (Cinvestav-IPN), Ciudad de México C.P. 07360, Mexico.
Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Ciudad de México C.P. 11340, Mexico.
Molecules. 2020 Feb 25;25(5):1020. doi: 10.3390/molecules25051020.
(-)-Epicatechin is a phenolic compound with antioxidant activity that is present in natural food and drinks, such as cocoa and red wine. Evidence suggests that (-)-epicatechin exhibits anticancer activity; however, its mechanism of action is poorly understood. Here, we investigated the anticancer effects of (-)-epicatechin and its mechanism of action in breast cancer cells. We assessed the anticancer activity by cell proliferation assays, apoptosis by DNA fragmentation and flow cytometry. The expression of proteins associated with apoptosis was analyzed by the human apoptosis array. MitoSOX Red and biomarkers of oxidative damage were used to measure the effect of (-)-epicatechin on mitochondrial reactive oxygen species (ROS) and cellular damage, respectively. (-)-Epicatechin treatment caused a decreasing in the viability of MDA-MB-231 and MCF-7 cells. This cell death was associated with DNA fragmentation and an apoptotic proteomic profile. Further, (-)-epicatechin in MDA-MB-231 cells upregulated death receptor (DR4/DR5), increased the ROS production, and modulated pro-apoptotic proteins. In MCF-7 cells, (-)-epicatechin did not involve death receptor; however, an increase in ROS and the upregulation of pro-apoptotic proteins (Bad and Bax) were observed. These changes were associated with the apoptosis activation through the intrinsic pathway. In conclusion, this study shows that (-)-epicatechin has anticancer activity in breast cancer cells and provides novel insight into the molecular mechanism of (-)-epicatechin to induce apoptosis.
（-）-表儿茶素是一种具有抗氧化活性的酚类化合物，存在于天然食品和饮料中，如可可和红酒。有证据表明（-）-表儿茶素具有抗癌活性；然而，其作用机制尚不清楚。在这里，我们研究了（-）-表儿茶素在乳腺癌细胞中的抗癌作用及其作用机制。我们通过细胞增殖测定、DNA 片段化和流式细胞术评估了抗癌活性。通过人类凋亡阵列分析了与凋亡相关的蛋白质的表达。使用 MitoSOX Red 和氧化损伤标志物分别测量（-）-表儿茶素对线粒体活性氧（ROS）和细胞损伤的影响。（-）-表儿茶素处理导致 MDA-MB-231 和 MCF-7 细胞活力下降。这种细胞死亡与 DNA 片段化和凋亡蛋白组学特征有关。此外，（-）-表儿茶素在 MDA-MB-231 细胞中上调了死亡受体（DR4/DR5），增加了 ROS 产生，并调节了促凋亡蛋白。在 MCF-7 细胞中，（-）-表儿茶素不涉及死亡受体；然而，观察到 ROS 增加和促凋亡蛋白（Bad 和 Bax）的上调。这些变化与通过内在途径激活细胞凋亡有关。总之，这项研究表明（-）-表儿茶素在乳腺癌细胞中具有抗癌活性，并为（-）-表儿茶素诱导细胞凋亡的分子机制提供了新的见解。
