Breast Cancer Subtypes Present a Differential Production of Reactive Oxygen Species (ROS) and Susceptibility to Antioxidant Treatment

• Main Authors: Fabiola Lilí Sarmiento-Salinas, Alam Delgado-Magallón, José Benito Montes-Alvarado, Dalia Ramírez-Ramírez, Juan Carlos Flores-Alonso, Paulina Cortés-Hernández, Julio Reyes-Leyva, Irma Herrera-Camacho, Maricruz Anaya-Ruiz, Rosana Pelayo, Lourdes Millán-Pérez-Peña, Paola Maycotte
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2019-06-01
• Series: Frontiers in Oncology
• Subjects: breast cancer; ROS; mitochondria; mitochondrial morphology; mitochondrial ROS
• Online Access: https://www.frontiersin.org/article/10.3389/fonc.2019.00480/full

Due to their crucial role in cell metabolism and homeostasis, alterations in mitochondrial biology and function have been related to the progression of diverse diseases including cancer. One of the consequences associated to mitochondrial dysfunction is the production of reactive oxygen species (ROS). ROS are known to have a controversial role during cancer initiation and progression and although several studies have tried to manipulate intracellular ROS levels using antioxidants or pro-oxidation conditions, it is not yet clear how to target oxidation for cancer therapy. In this study, we found differences in mitochondrial morphology in breast cancer cells when compared to a non-tumorigenic cell line and differences in mitochondrial function among breast cancer subtypes when exploring gene-expression data from the TCGA tumor dataset. Interestingly, we found increased ROS levels in triple negative breast cancer (TNBC) cell lines and a dependency on ROS for survival since antioxidant treatment induced cell death in TNBC cells but not in an estrogen receptor positive (ER+) cell line. Moreover, we identified the mitochondria as the main source of ROS in TNBC cell lines. Our results indicate a potential use for ROS as a target for therapy in the TNBC subtype which currently has the worst prognosis among all breast cancers and remains as the only breast cancer subtype which lacks a targeted therapy.