Figure 3 | Cell Death & Disease

Figure 3

From: Mitochondrial protection impairs BET bromodomain inhibitor-mediated cell death and provides rationale for combination therapeutic strategies

Figure 3

Mitochondrial damage is necessary to induce I-BET762-mediated apoptosis. (a) Eμ-myc/Bcl-2 lymphomas were treated as indicated with 0.5 μM I-BET762. (Inset) Clonogenic assay with Eμ-myc/Bcl-2 lymphomas after being pretreated for 48 h with DMSO or I-BET762 and then seeded in soft agar. Colonies have been counted after 12 days in culture. (b– d) Retuximab/chemoresistant human lymphoma models (4RH) were treated for 240 h with indicated concentrations of I-BET762. Apoptosis was assessed by flow cytometric analysis of TMRE, surface exposure of phosphotidylserine (annexin V staining) and cell-cycle analysis. (e) MTS assay to evaluate the proliferation rate of all four lymphoma models in the presence or absence of the I-BET762 over time. Each point represents the mean value of three individual experiments ±S.E. (f) Western blot analysis on whole-cell lysates prepared from Eμ-myc/Bcl-2 cell line treated for 24 h and (g) Raji-4RH and RL-4RH lymphomas treated for 72 h with the indicated doses of I-BET762 or DMSO. The expression of indicated proteins was detected with specific antibodies and loading normalization was confirmed by GAPDH probing

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