Curcumin and Berberine as Potential Therapeutic Agents Targeting ACSL4-Mediated Ferroptosis in Glioblastoma 2258063

Abstract

Abstract Introduction Glioblastoma multiforme (GBM) remains one of the most aggressive and treatment-resistant brain cancers. Despite advances in surgery and chemoradiation, long-term survival remains poor, underscoring the need for novel therapeutic approaches. Natural bioactive compounds such as curcumin and berberine have shown promise as anticancer agents through their ability to modulate oxidative stress and programmed cell death. ACSL4, a lipid-metabolizing enzyme essential for ferroptosis, has emerged as a molecular target that regulates glioblastoma cell survival. This study investigates whether curcumin and berberine can trigger ACSL4-associated ferroptotic cell death in GBM, offering a potential translational pathway for therapeutic development. Methods U87MG glioblastoma cells were cultured and treated with curcumin or berberine. Cell viability was measured using standard assays, and ongoing work includes assessing ACSL4 expression and markers of ferroptosis to clarify drug-specific mechanisms. Co-treatment experiments are being performed to evaluate whether combining curcumin and berberine enhances therapeutic efficacy. Results Curcumin treatment reduced GBM cell viability, suggesting cytotoxic activity consistent with ferroptotic cell death. Preliminary studies indicate that berberine produces a complementary reduction in viability, and combined treatment may produce additive effects. Further analysis of ACSL4 expression and lipid peroxidation is underway to confirm whether both compounds act through ferroptosis-associated mechanisms. Conclusion These findings support the potential of curcumin and berberine as therapeutic agents for glioblastoma through targeting ACSL4-mediated ferroptosis. Continued mechanistic analysis will help establish whether these natural compounds can be developed as adjunctive treatments for resistant brain tumors. Funding Source n/a Topic Categories Translational and Interventional Immunology (TI)