The protozoan inhibitor Atovaquone affects mitochondrial respiration and shows in vitro efficacy against glucocorticoid-resistant cells in childhood B-cell acute lymphoblastic leukaemia

Atovaquone is a well-tolerated drug used in the clinic mainly against malaria. Being a ubiquinone analogue, this drug inhibits co-enzyme Q10 of the electron transport chain (ETC) affecting oxidative phosphorylation and cell metabolism. In this study we tested the effect of Atovaquone on cALL cells in vitro. The outcome of this inhibition of the ETC is a marked decrease in basal respiration and ATP levels, as well as reduced proliferation, cell cycle arrest and induction of apoptosis. On the transcriptional level, we see changes in cellular metabolic processes, activation of p53 pathway, apoptosis, enrichment of cell cycles genes and downregulation of hypoxia and mTORC1 signalling pathway. Comparing biological triplicates of untreated and treated with Atovaquone REH cells (72h).