fig4

Statins markedly potentiate aminopeptidase inhibitor activity against (drug-resistant) human acute myeloid leukemia cells

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.

Cancer Drug Resistance
ISSN 2578-532X (Online)

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