Fig. 6

Ascorbic acid synergistically increases the effects of targeted therapies on CLL B-cells. a: Viability of CLL B-cells treated with 250 μM AA alone or in combination with the approved drugs fludarabine (35 μM) and cyclophosphamide (100 μM) (n = 6), ibrutinib (15 μM) (n = 11), idelalisib (50 μM) (n = 12), and venetoclax (10 nM) (n = 16)) (*: p < 0.05; **: p < 0.01, ***: p < 0.001). Cell viability was determined by an annexin V/7AAD staining. b: Synergistic efficacy of combination of AA and CLL targeted therapies in primary CLL B-cells. Left panels: Primary CLL cells (n = 6) were treated with ascorbic acid (AA) and ibrutinib or idelalisib or venetoclax for 24 h. CellTiter-Glo cell viability assay was performed to detect cell kill synergy. The curves show the dose-effect of single drugs and that of drugs combination. Each data point is the mean of six samples. Right panels: Tables show the combination index (CI) of each combination for each patient (P). The CI values were calculated using the Chou-Talalay method by the software Compusyn. Fa: fraction affected (fraction of cells affected by a particular drug dose)