fig4

Figure 4. Simvastatin potentiation of CHR2863 activity in human AML cell lines vs. human lymphoid and solid tumor cell lines. Cell growth inhibition was determined after 72 h of drug exposure in the absence or presence of maximal non-toxic concentrations of simvastatin, being (between brackets) for: U937 (2 µM), THP1 (2.5 µM), MV4-11 (2.5 µM), KG1 (10 µM), CCRF-CEM (2.5 µM), CEM/Vbl (2.5 µM), SW1573 (0.2 µM), 2008 (0.75 µM), 2008/MRP1 (2.5 µM), MCF7 (1 µM), MCF7/MR (2.5 µM) and KB (1 µM). Simvastatin potentiation factor is defined as the ratio of IC₅₀ (50% growth inhibition) of cell culture without statins vs. IC₅₀ of cell cultures in the presence of statins. IC₅₀ values (between brackets) for CHR2863 for the various cell lines (in the absence of simvastatin) were: U937 (61 ± 16 nM), THP1 (1172 ± 807 nM), MV4-11 (282 ± 51 nM), KG1 (394 ± 144 nM), CCRF-CEM (11,170 ± 5,100 nM), CEM/Vbl (29,100 ± 5,900 nM), SW1573 (6,625 ± 3,020 nM), 2008 (2,020 ± 1,080 nM), 2008/MRP1 (6,700 ± 2,560 nM), MCF7 (453 ± 400 nM), MCF7/MR (386 ± 64 nM), and KB (132 ± 50 nM). The results depicted are the mean ± SD of 3-5 independent experiments. CHR2863: (6S)-[(R)-2-((S)-Hydroxy-hydroxycarbamoyl-methoxy-methyl)-4-methyl-pentanoylamino]-3,3 dimethyl-butyric acid cyclopentyl ester.