Fig. 3

GLS1 inhibition by BPTES sensitizes PDA to ß-lap in an NQO1-dependent manner. a Clonogenic survival assay of MiaPaCa2 pre-treated ± 500 nM BPTES for 48 h followed by the addition of ß-lap ±50 μM for 2 h. Data represent survival means ± SE from quadruplicate samples. b MiaPaCa2 cells treated with 100 μM of the GLUD1 inhibitor, EGCG, for 48 h followed by 2-h ß-lap dose response. Relative cell viability represents mean of CellTiter-Glo survival assay 48 h after ß-lap treatment plotted as percentage treated/control (T/C) ± SE from sextuplicate samples. c Clonogenic survival assay of normal lung fibroblast cell line, IMR90, pre-treated with ±500 nM BPTES for 48 h followed by 2 h of ß-lap treatment. Data represent survival means ± SE from quadruplicate samples. d MiaPaCa2, ASPC1, and HPAFII PDA cell lines were pre-treated with ± 500 nM BPTES for 48 h, either 3 mM oxaloacetate (OAA) or 3 mM dimethyl malate for the last 24 h, and 2.5 μM ß-lap for 2 h. Relative cell viability represents means of CellTiter-Glo survival assay 48 h after treatment plotted as percentage (T/C) ± SE from sextuplicate samples. e Various cancer cell lines pre-treated with ± 500 nM BPTES (sub-growth inhibitory) for 48 h followed by the addition of 2.5 μM ß-lap for 2 h. Mutant (mt) KRAS lines: A549 non-small cell lung (NSCL), PL45 PDA, NQO1 expressing S2-013 (S2+) PDA, NQO1 expressing MDA-MB-231 (231+) triple-negative breast, H2122 NSCL, NQO1-deficient S2-013 (S2−) PDA, and NQO1 deficient MDA-MB-231 (231−) triple-negative breast cancer cells. Wild-type (wt) KRAS lines: Hs766T PDA, BxPC3 PDA, MCF7 breast, as well as NQO1+ H596 NSCL and H661 NSCL cancer cell lines