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. Author manuscript; available in PMC: 2019 Aug 16.
Published in final edited form as: Cell Chem Biol. 2018 Jun 14;25(8):996–1005.e4. doi: 10.1016/j.chembiol.2018.05.008

Figure 2.

Figure 2

PAC-1 combination therapies lead to caspase-3 activation and degradation of MEK1 and MEK2 kinases. (A) Procaspase-3 activation leads to dramatic reduction in MEK1 and MEK2 levels in A375 and SK-MEL-5 cells treated with PAC-1 (5 μM) + vemurafenib (10 μM) for 48 hours. This reduction was not observed in cells treated with trametinib (30 nM) + vemurafenib. (B) H1975 and PC-9 GR cells treated with PAC-1 (5 μM) + osimertinib (4 nM) for 48 hours led to procaspase-3 activation and corresponding degradation of MEK1 and MEK2 kinases. This was not observed in cells treated with PAC-1 + gefitinib (4 nM) or trametinib (30 nM) + osimertinib. (C) MEK1 and MEK2 degradation were similarly observed in H3122 cells treated with PAC-1 (5 μM) + ceritinib (30 nM) for 48 hours but not in cells treated with trametinib (30 nM) + ceritinib. See also Figure S2 and S3.