Dehydroleucodine exerts an antiproliferative effect on human Burkitt's lymphoma Daudi cells via SLC7A11-mediated ferroptosis.

BACKGROUND: Burkitt's lymphoma (BL) is a rare, highly aggressive B-cell non-Hodgkin's lymphoma known for rapid proliferation. While most patients respond well to intensive chemotherapy, those who are older, have comorbidities, or develop therapy resistance show limited outcomes. PURPOSE: This study aims to evaluate the in vitro anti-tumor activity of dehydroleucodine (DhL), a novel plant-derived chemotherapeutic agent, against BL cells and to elucidate the molecular mechanisms underlying its effects. METHODS: A screening of 42 plant-derived small molecules identified DhL as a potent inhibitor of BL growth. We evaluated DhL's effects on cell cycle progression, apoptosis, and ferroptosis pathways using cell viability assays, flow cytometry, transcriptomic analysis, and validation experiments. RESULTS: DhL demonstrated robust and specific anti-proliferative effects against BL Daudi cells. Mechanistic investigations revealed that DhL exerts its effects through cell cycle modulation, induction of apoptosis, and ferroptosis. Transcriptomic analysis identified SLC7A11 as a critical regulator of DhL-mediated ferroptosis, which was further validated experimentally. CONCLUSION: DhL shows strong potential as a novel chemotherapeutic agent for BL treatment by targeting SLC7A11-mediated ferroptosis. Further investigation is warranted to confirm its efficacy and clinical utility in diverse BL patient populations.