Fig. 6: Reshaping succinate metabolism by fludarabine can antagonize drug resistance in AML cells. | Nature Communications

Fig. 6: Reshaping succinate metabolism by fludarabine can antagonize drug resistance in AML cells.

From: Succinate dehydrogenase deficiency-driven succinate accumulation induces drug resistance in acute myeloid leukemia via ubiquitin-cullin regulation

Fig. 6

a H1299 cells were treated with 82 FDA approved anti-cancer drugs for three days (25% PPC). The final relative succinate Level= the succinate level /the survival rate. b HL-60 cells were treated with the top7 drugs (25 % PPC, three days) in Fig. 6a. Two independent experiments were performed; Data are presented as mean (n = 2). c shCtrl and shSDHA HL-60 cells were treated with 500 nM fludarabine for three days. d Detection of UBC12 phosphorylation in HL-60 cells after treated with 500 nM fludarabine for three days, followed by treatment of 6 mM succinate for 3 h before collecting the samples. The samples derive from the same experiment but different gels for p-UBC12 and another for UBC12 were processed in parallel. e Detection of cullin neddylation in HL-60 cells after treated with 500 nM fludarabine for three days, followed by treatment of 6 mM succinate for indicated time before collecting the samples. The samples derive from the same experiment but different gels for cul1 and another for cul3 were processed in parallel. f–g shCtrl and shSDHA HL-60 cells were treated with fludarabine (f) and CB-839 (g) for three days respectively. h shCtrl and shSDHA HL-60 cells were seeded in soft agar, followed by treatment with 200 nM fludarabine. After two weeks, the clones were stained and counted. i, shCtrl and shSDHA HL-60 cells were treated with 500 nM fludarabine for three days, and the apoptosis rates were detected. j Detection of intracellular succinate levels (left) and cell viability (right) of HL-60 shSDHA cells after treated by a series of concentrations of fludarabine for three days. k–l Cytarabine, IDA or fludarabine were treated individually or in combination to indicated cells for three days. IDA: idarubicin HCl. c, f–l Three independent experiments were performed. Data are presented as mean ± SD (n = 3); The significance analysis were conducted by two-tailed Student’s t-test or one-way ANOVA for Fig. 6c, f–l. Source data are provided as a Source Data file.

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