Figure 2.
BET inhibition sensitizes DLBCL cell lines to ferroptosis induction. (A) DOHH2 and SU-DHL-6 cells were treated with DMF alone (left panels) or in combination with JQ1 (right panels), as indicated. Cells were treated with JQ1 for 24 hours before incubation with DMF for another 24 hours. Cell numbers were determined and the combination treatments were normalized to the respective DMF single treatment. The CI for 20 μM DMF and 0.25 μM JQ1 in DOHH2 and SU-DHL-6 cells is 0.26 and 0.46, respectively. (B) The survival of BRD4-silenced DOHH2 cells in response to daily DMF treatment was determined after 3 days and normalized to control cells transduced with a nontargeting shRNA. (C) DOHH2 cells were treated with 0.25 μM JQ1 or 0.25 μM I-BET151 for 24 hours before adding 10 μM DMF alone or in combination with 10 μM ferrostatin-1 (Fer-1), 100 μM α-tocopherol (α-Toco), 100 μM deferoxamine (DFX), 25 μM N-acetyl-L-cysteine (NAC), and 10 μM Q-VD-OPh for another 24 hours, as indicated. After 48 hours, cell numbers were determined. Dotted line marks cell survival upon single treatment with BETi. (D) DOHH2 and SU-DHL-6 cell were treated with JQ1 and RSL3 either alone or in combination for 48 hours before quantifying cell survival. The combination treatments were normalized to the respective RSL3 single treatment. The CI in DOHH2 cells was 0.16 (for 0.05 μM RSL3 and 0.1 μM JQ1) and in SU-DHL-6 cells 0.13 (for 0.01 μM RSL3 and 0.1 μM JQ1). (E) DOHH2, SU-DHL-4, and SU-DHL-6 cells were treated with solvent, LDC067, DMF, or the indicated combinations. Lipid peroxidation was analyzed by flow cytometry. (F) DOHH2 and SU-DHL-6 cells were treated with DMF (left panels) alone or in combination with LDC067 (right panels), as indicated. Cell survival was quantified after 48 hours of treatment. The CI in DOHH2 cells was 0.60 (for 10 μM DMF and 5 μM LDC067) and in SU-DHL-6 cells 0.51 (for 20 μM DMF and 2.5 μM LDC067). Error bars correspond to the mean ± SD. Data are representative of at least 3 (A,D-F) or 2 (B-C) independent experiments. ∗P < .05; ∗∗P < .01; ∗∗∗P < .005. CI, combination index.

BET inhibition sensitizes DLBCL cell lines to ferroptosis induction. (A) DOHH2 and SU-DHL-6 cells were treated with DMF alone (left panels) or in combination with JQ1 (right panels), as indicated. Cells were treated with JQ1 for 24 hours before incubation with DMF for another 24 hours. Cell numbers were determined and the combination treatments were normalized to the respective DMF single treatment. The CI for 20 μM DMF and 0.25 μM JQ1 in DOHH2 and SU-DHL-6 cells is 0.26 and 0.46, respectively. (B) The survival of BRD4-silenced DOHH2 cells in response to daily DMF treatment was determined after 3 days and normalized to control cells transduced with a nontargeting shRNA. (C) DOHH2 cells were treated with 0.25 μM JQ1 or 0.25 μM I-BET151 for 24 hours before adding 10 μM DMF alone or in combination with 10 μM ferrostatin-1 (Fer-1), 100 μM α-tocopherol (α-Toco), 100 μM deferoxamine (DFX), 25 μM N-acetyl-L-cysteine (NAC), and 10 μM Q-VD-OPh for another 24 hours, as indicated. After 48 hours, cell numbers were determined. Dotted line marks cell survival upon single treatment with BETi. (D) DOHH2 and SU-DHL-6 cell were treated with JQ1 and RSL3 either alone or in combination for 48 hours before quantifying cell survival. The combination treatments were normalized to the respective RSL3 single treatment. The CI in DOHH2 cells was 0.16 (for 0.05 μM RSL3 and 0.1 μM JQ1) and in SU-DHL-6 cells 0.13 (for 0.01 μM RSL3 and 0.1 μM JQ1). (E) DOHH2, SU-DHL-4, and SU-DHL-6 cells were treated with solvent, LDC067, DMF, or the indicated combinations. Lipid peroxidation was analyzed by flow cytometry. (F) DOHH2 and SU-DHL-6 cells were treated with DMF (left panels) alone or in combination with LDC067 (right panels), as indicated. Cell survival was quantified after 48 hours of treatment. The CI in DOHH2 cells was 0.60 (for 10 μM DMF and 5 μM LDC067) and in SU-DHL-6 cells 0.51 (for 20 μM DMF and 2.5 μM LDC067). Error bars correspond to the mean ± SD. Data are representative of at least 3 (A,D-F) or 2 (B-C) independent experiments. ∗P < .05; ∗∗P < .01; ∗∗∗P < .005. CI, combination index.

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