BET inhibition amplifies DMF-induced lipid peroxidation in DLBCL. (A) Experimental setup of the compound library screen comprising epigenetic modulators used for the identification of ferroptosis-sensitizing agents. (B) DOHH2 cells were treated with the indicated compounds for 24 hours and subsequently incubated with DMF for 2 hours. Lipid peroxidation was quantified by flow cytometry using the oxidation-sensitive fluorescent probe BODIPY C11 and normalized to the solvent control. (C) DOHH2 cells were treated with the indicated BETis for 24 hours and DMF for an additional 2 hours before analyzing lipid peroxidation by flow cytometry. (D) The indicated GCB-DLBCL cell lines were treated with either JQ1, DMF, or the combination of both compounds. Lipid peroxidation was assessed using flow cytometry. (E) Quantification of lipid peroxidation in DOHH2 cells that were treated with JQ1 or I-BET151 for 24 hours and RSL3 for another 2 hours. The mean fluorescence intensity (MFI) of oxidized BODIPY C11 in treated cells was normalized to the MFI of the solvent control. (F) Lipid peroxidation of DMF-treated control and BRD4-silenced DOHH2 cells was analyzed using flow cytometry. Error bars correspond to the mean ± standard deviations (SD). Data are representative of at least 3 (C-E) or 2 (F) independent experiments. ∗P < .05; ∗∗∗P < .005.