Apoptosis Induced by (−)-Epicatechin in Human Breast Cancer Cells is Mediated by Reactive Oxygen Species

Molecules

JuanPedro Luna-Arias¹  Fernando Pereyra-Vergara¹  AdrianaGuadalupe Perez-Ruiz²  JoséRubén García-Sánchez²  IvonneMaría Olivares-Corichi² 

[1] Departamento de Biología Celular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (Cinvestav-IPN), Ciudad de Mexico C.P. 07360, Mexico;Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Ciudad de Mexico C.P. 11340, Mexico;

关键词: apoptosis;    breast cancer;    reactive oxygen species;    (−)-epicatechin;   

DOI  :  10.3390/molecules25051020

来源: DOAJ

【 摘 要 】

(−)-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^TM 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.

【 授权许可】

Unknown