TY - JOUR
T1 - Apoptosis induced by (−)-epicatechin in human breast cancer cells is mediated by reactive oxygen species
AU - Pereyra-Vergara, Fernando
AU - Olivares-Corichi, Ivonne María
AU - Perez-Ruiz, Adriana Guadalupe
AU - Luna-Arias, Juan Pedro
AU - García-Sánchez, José Rubén
N1 - Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
PY - 2020/2/25
Y1 - 2020/2/25
N2 - (−)-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. MitoSOXTM 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.
AB - (−)-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. MitoSOXTM 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.
KW - (−)-epicatechin
KW - Apoptosis
KW - Breast cancer
KW - Reactive oxygen species
UR - http://www.scopus.com/inward/record.url?scp=85081225929&partnerID=8YFLogxK
U2 - 10.3390/molecules25051020
DO - 10.3390/molecules25051020
M3 - Artículo
C2 - 32106523
AN - SCOPUS:85081225929
SN - 1420-3049
VL - 25
JO - Molecules
JF - Molecules
IS - 5
M1 - 1020
ER -