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[Preprint]. 2023 Jul 28:2023.07.26.550731. [Version 1] doi: 10.1101/2023.07.26.550731

Figure 1. Culture in HPLM changes sensitivity to a variety of therapeutic agents.

Figure 1.

(A) Percent difference in the area under curve (% Difference in AUC) data for SUM149 cells cultured in either RPMI or HPLM after treatment with anti-cancer and metabolic inhibitor libraries. Only compounds with an Emax >50% in either medium are shown. (B) The same data as in (A) categorized based on target pathway. (C – F) Dose-response curves of the purine biosynthesis inhibitors lometrexol (C), azathioprine (D), 6-mercaptopurine (E), and 6-thioguanine (F) on SUM149 cells growing in RPMI vs HPLM. (G & H) Growth curves of HCC1806 (G) and SUM149 (H) cells treated with lometrexol in RPMI vs HPLM. (I) LC-MS analysis to quantify purine nucleotide abundance in HCC1806 cells treated with lometrexol in RPMI vs HPLM. * indicates p < 0.05 for HPLM + lometrexol relative to RPMI + lometrexol (unpaired two-tailed t-test). (J) Schematic representation of purine synthesis and salvage pathways. (K – N) Dose-response curves of the purine biosynthesis inhibitors lometrexol (K), azathioprine (L), 6-mercaptopurine (M), and 6-thioguanine (N) on SUM149 cells grown in RPMI with and without hypoxanthine (HXN). (O – R) Dose-response curves of the purine biosynthesis inhibitors lometrexol (O), azathioprine (P), 6-mercaptopurine (Q), and 6-thioguanine (R) on SUM149 cells grown in HPLM with and without hypoxanthine (HXN). For all panels data represents the means ± SD of triplicate samples.