Fig. 3
Pyruvate secreted by TNBC cell lines reduces the potency of CB-839. a Pharmacological MCT1 inhibition using 1 μM AZD3965 reduced the secretion of pyruvate by Hs578T and SUM159PT (SUM159) but not MDA-MB-231-luc-D3H2LN (D3H2LN) cells. Pyruvate concentration in the conditioned or unconditioned RPMI 1640 + 5% FBS (RPMI) culture medium was quantified after 48 h incubation (mean ± SEM, n = 3, t test). b The pyruvate concentration in the conditioned culture medium from a correlates with resistance of recipient MDA-MB-231 cells to CB-839-treatment at 10 nM, 100 nM, 1 μM or 10 μM over 3 days exposure. For each of the TNBC cell lines studied the AZD3965-treated samples of conditioned culture medium demonstrated a decrease in relative thymidine incorporation in recipient MDA-MB-231 cells (mean ± SD, n = 2). c IC50 analysis also demonstrates a correlation between CB-839 sensitivity and pyruvate concentration in the conditioned culture medium from a (mean ± SD, n = 2). Correlations were computed by Pearson r correlation coefficient analysis