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. Author manuscript; available in PMC: 2017 Mar 27.
Published in final edited form as: ACS Chem Biol. 2016 Oct 17;11(11):3214–3225. doi: 10.1021/acschembio.6b00651

Figure 5. ML385 is selectively toxic to cells with KEAP1 mutations and potentiates the toxicity of chemotherapy drugs in NSCLC cells with KEAP1 mutations.

Figure 5

(a) H460, a NSCLC line with a point mutation in KEAP1, is more sensitive to ML385 than H460-KEAP1 Knock-in H460 cells expressing WT KEAP1. ‘*’P<0.05 relative to H460-KEAP1 Knock-in cells. (b) Treatment with ML385 selectively inhibits the colony forming ability of lung cancer cells but has no effect on the growth of non-tumorigenic BEAS2B cells. (c–d) H460 and A549 cells were treated with different concentrations of paclitaxel, doxorubicin, or carboplatin alone or in combination with ML385 for 72 h. At the end of treatment, regular growth medium was added and cells were further incubated for 8–10 days and stained with crystal violet. (e) H460 cells treated with ML385 in combination with chemotherapy drug showed increased caspase 3/7 activity, a marker of apoptosis. Cells treated with chemotherapy drug alone or ML385 in combination with chemotherapy drug were incubated with luminogenic caspase substrate and change in luminescence was measured. Caspase activity was normalized to the number of viable cells using CellTiter-Blue assay. Error bars represent ±S.D. ‘*’P<0.05 relative to vehicle or ML385; ‘**’ P<0.05 relative to chemotherapy drug alone.