Decitabine synergizes with a novel complex I inhibitor to inhibit the growth of cell lines and primary MCL cells
(A) Highest single agent synergy scores of decitabine and IM156, an inhibitor of mitochondrial complex I, in MCL cell lines. A 4 × 4 matrix of 2 drugs and all of the possible combinations were designed on a 96-well plate. Synergy scores were calculated using SynergyFinder+.
(B) Decitabine and IM156 synergized to inhibit primary MCL cells.
(C) Decitabine and IM156 did not synergistically kill normal B cells.ns, not significant.
(D) MCL cells were pretreated with gamitrinib (1.25 μM) or solvent control for 4 days; fresh drug was added every 2 days. Drug/solvent control was removed on day 4. Cells were incubated in normal growth media for 24 h before treatment with decitabine, IM156, or the combination of both drugs at indicated concentrations in a 96-well plate. On day 3 of treatment, cell viability was measured using CellTiter Glo. Error bars represent mean ± SD (Student’s t test). All of the experiments were performed independently twice, except for primary normal B cells, each with 3 technical replicates.