Dehydroleucodine Exerts an Antiproliferative Effect on Human Burkitt's Lymphoma Daudi Cells via SLC7A11-mediated Ferroptosis

Burkitt's lymphoma (BL) is a rare, highly aggressive B-cell non-Hodgkin's lymphoma characterized by rapid proliferation. Despite favorable outcomes for the majority of patients treated with intensive chemotherapy regimens, older patients, those with comorbidities, and those exhibiting therapy resistance continue to experience poor prognoses. In the present study, we investigate the in vitro anti-tumor activity of dehydroleucodine (DhL), a novel chemotherapeutic agent, against BL cells and explore the molecular mechanisms which are fundamental to its actions. DhL, identified through screening of 42 plant-derived small molecule compounds, demonstrated potent and specific anti-proliferative effects against BL Daudi cells. We further showed that the mechanism of action of DhL involves cell cycle modulation, induction of apoptosis, and, notably, the induction of ferroptosis. Transcriptomic analysis and subsequent experimentation revealed that DhL-mediated ferroptosis is dependent on SLC7A11, a key regulator of this specific cell death pathway. Overall, these observations highlight the potential of DhL as a promising chemotherapeutic agent for the treatment of BL.