The Hemerocallis citrina extracts ameliorate radiation-induced ferroptosis in LO2 cells through the Nrf2-xCT/GPX4 pathway

Abstract

Radiotherapy, a primary approach in cancer treatment, damages normal cells while targeting cancer cells. Therefore, it is crucial to identify drugs with minimal side effects, high reliability, and radioprotective effects to develop novel radiotherapy strategies. Hemerocallis citrina extracts (HCE), which are derived from plants with medicinal and culinary applications, possess antioxidative and anticancer properties. In this study, we investigated the radioprotective effects of HCE on LO2 cells exposed to radiation to determine whether these effects were mediated through the nuclear factor erythroid 2-related factor 2-cystine–glutamate antiporter/glutathione peroxidase 4 pathway. Cell proliferation experiments demonstrated the radioprotective effect of HCE on LO2 cells. Western blot analysis revealed that HCE regulated B-cell lymphoma protein 2-associated X, Cleaved-caspase 3, and B-cell lymphoma protein 2, thereby inhibiting radiation-induced apoptosis, which was consistent with the flow cytometry results. Moreover, the detection of ferroptosis-related markers indicated that HCE alleviated radiation-induced ferroptosis in LO2 cells through the nuclear factor erythroid 2-related factor 2-cystine–glutamate antiporter/glutathione peroxidase 4 pathway. These findings provide a theoretical basis for the radioprotective effects of HCE on LO2 cells and offer new insights into the development of radioprotective drugs. Graphical abstract: http://links.lww.com/AHM/A122.