Fig. 7

The organometallic nucleosides induce a rapid mitochondrial depolarization in primary CLL cells. (a) Respiration (oxygen consumption rate; OCR) is measured in primary CLL cells (n = 3) under basal conditions and in response to 10 μM fludarabine, 25 μM bendamustine, and 10 μM of the 3 most active metal containing nucleoside analogues (MCNA) in addition to a condition of 3 μM of the electron transport chain inhibitors antimycin A/rotenone (specifically block mitochondrial respiration). OCR quickly and drastically drops after exposure to the MCNA, but not after bendamustine or fludarabine. Percentages of OCR as compared to the baseline measurement (“before injection”, set as 100 %) are shown. (b) The mitochondrial electrochemical membrane potential (∆ΨM) was semi-quantified in primary CLL-cells (n = 3) by flow cytometry using the potentiometric dye JC-1. Histograms of a representative donor are shown in Additional file 1 Fig. S9. Changes in JC-1 mean fluorescence index (MFI) were assessed upon treatment with 10 μM fludarabine, or 25 μM bendamustine, or 10 μM of each of the 3 most active MCNA. FCCP (1.5 μM) an ionophore uncoupler was used as a positive control for reducing the mitochondrial membrane potential and accordingly JC-1 staining. The MCNA, but neither fludarabine nor bendamustine, induce marked decreases in ∆ΨM. Summarized results represent percentages of the MFI of untreated control cells (set as 100 %). Significance levels: *P ≤ 0.05; ** P = 0.002