LAUSR

CONTEXT Breast cancer (BC) is the most prevalent diagnosed tumour and the major reason of tumour-related death in females around the world. Isoliquiritin, a type of plant extract, has exhibited the probable inhibitory effect in a variety of cancers. However, the anti-tumour effect on the BC is still unclear. OBJECTIVE To reveal the effect and potential mechanism of Isoliquiritin on BC. MATERIALS AND METHODS The cell viabilities were detected by CCK-8 assay. The levels of indicators of ferroptosis, oxidative stress, glycolysis and inflammation were evaluated by commercial kits, flow cytometry, western blot, spectrophotometry and ELISA assays. Mechanically, the expressions expression of NF-κB pathway were determined by western blot. In vivo assay was also yielded on the BALB/c nude mice. RESULTS Iso induced a concentration and time-dependent decrease of viability in both MDA-MB-231 and MCF-7 cells. Iso treatment significantly increased the levels of Fe2+, ROS and MDA, and decreased the GSH level, and the relative protein expressions of GPX4 and xCT. Furthermore, Iso modulated the oxidative stress, glycolysis and inflammation through ferroptosis. In addition, Iso induced a concentration-dependent decrease of cell viability and a concentration-dependent increase of apoptosis rate in both MDA-MB-231/Dox and MCF-7/Dox cells. Iso notably counteracted the LPS-induced the relative protein levels of p-p50/p50, p-p65/p65 and IκB, and the levels of ferroptosis, oxidative stress, glycolysis and inflammation. The same results were also verified in vivo. CONCLUSION Iso inhibited the NF-κB signalling to regulate ferroptosis and improved Dox-resistance in breast cancer.