Pro-oxidant effect of lobaric acid as a therapeutic strategy against breast cancer: a molecular perspective

Background: This study aimed to investigate the anticancer effects of lobaric acid (LA), a lichen acid, in MCF-7 cells. Our previous study demonstrated that LA exhibits anticancer effects by triggering apoptosis in MCF-7 cells. However, the relationship between this anticancer effect and the oxidative pathway and apoptosis mechanism has not been explained. In this study, the cytotoxic and anticancer effects of LA on MCF-7 cells were investigated through oxidative stress and thioredoxin system pathways. Methods and results: For this purpose, reactive oxygen species (ROS), reduced glutathione (GSH), and malondialdehyde (MDA) levels were measured in MCF-7 cells exposed to LA at a concentration of 44.21 µg/mL (IC50). Additionally, the activities, gene, and protein levels of SOD, CAT, GPx, GST, GR, and TrxR enzymes were evaluated. In addition, the expression levels of TXN and TXNIP genes were also analyzed. The results showed that LA increased ROS and MDA levels and decreased GSH levels. Antioxidant enzyme activities (SOD, CAT, GR, TrxR) and protein levels decreased compared to the control, while heterogeneous changes were observed in gene expression levels. Despite increased GPX gene expression, a decrease in enzyme activity and protein levels was observed. While no change in TXN gene expression was observed, protein levels were decreased. TXNIP protein levels were also decreased. Conclusions: The findings provide important data for evaluating lichen-derived compounds as potential anticancer agents targeting redox balance.