The curcumin derivative DMC-GF promotes ferroptosis through the Nrf2/HMOX1 pathway, increasing glioma susceptibility to temozolomide

Glioblastoma (GBM) is a highly deadly primary brain tumor, and the conventional chemotherapeutic treatment temozolomide (TMZ) often experiences therapeutic failure due to the development of drug resistance. Therefore, innovative techniques that can overcome resistance and enhance TMZ efficacy are urgently needed (Wu et al. Pharmacol Res 171: 105780, 2021). This study examined the anticancer efficacy and mechanisms of the newly synthesized curcumin derivative DMC GF in glioma cells. Our findings indicate that DMC GF effectively activates the Nrf2/HMOX1 signaling pathway, consequently inducing ferroptosis while simultaneously inhibiting glioma cell proliferation and malignant advancement (Bebber et al. Cancers (Basel) 12, 2020). Comprehensive mechanistic analyses demonstrate that DMC GF-induced ferroptosis displays the characteristic features of this controlled form of cell death. Furthermore, DMC GF synergistically amplifies the cytotoxic efficacy of TMZ in vitro. This is the inaugural research demonstrating that DMC GF induces anti-GBM activity via ferroptosis and significantly enhances TMZ sensitivity. DMC GF presents itself as a prospective therapeutic candidate for GBM and a possible sensitizer to TMZ, providing a novel approach for combined therapy in clinical applications.