Redox homeostasis of breast cancer lineages contributes to differential cell death response to exogenous hydrogen peroxide.

Abstract Aims Cancer cells produce higher amounts of reactive oxygen species (ROS) than their normal counterparts. It has been suggested that a further increase in ROS concentration in these cells would lead to oxidative damage-driven death. Thus, we aimed to understand how the intra- and extracellular redox homeostasis differences set cell death response to ROS in breast cancer cell lines. Main methods Intra- and extracellular ROS generation was evaluated in tumoral (MCF-7 and MDA-MB-231) and non-tumoral (MCF10A) breast epithelial cells, as well as H 2 O 2 concentration in the culture medium, glutathione peroxidase (GPx), total superoxide dismutase (SOD) and catalase activities, extracellular H 2 O 2 scavenging capacity and total thiol content. Cell viability was determined after H 2 O 2 exposure using the MTT assay. Key findings We have found an increased extracellular ROS production in tumor cells when compared to the non-tumoral lineage. MCF10A cells had higher H 2 O 2 concentration in the extracellular medium. Moreover, extracellular H 2 O 2 -scavenging activity was higher in MDA-MB-231 when compared to MCF10A and MCF-7. Regarding intracellular antioxidant activity, a lower GPx activity in tumor cell lines and a higher catalase activity in MDA-MB-231 were observed. Thiol content was lower in MDA-MB-231. Additionally, tumor cell lines were more sensitive to H 2 O 2 exposure than the non-tumoral cells. Significance The present report shows that the capability to generate and metabolize ROS differ greatly among the breast cancer cell lines, thus suggesting that redox balance is finely regulated during carcinogenesis. Therefore, our data suggest that therapeutic approaches targeting the redox status might be useful in the treatment of breast tumors.