Figure 1 from N-Myristoytransferase Inhibition Causes Mitochondrial Iron Overload and Parthanatos in TIM17A-Dependent Aggressive Lung Carcinoma

Lung carcinoma cells with LKB1 and/or KEAP1 mutations in a KRAS-mutant background are sensitive to myristoylation inhibition. A, NMTi IC₅₀ for lung carcinoma cells with the indicated mutational status were compared. IC₅₀ values for ICL1100013 (DDD85646) were from Genomics of Drug Sensitivity in Cancer and mutational profiles from DepMap. **, P = 0.008; *, P = 0.005; ns = not significant (Student t test). Crossbar, median. B, Viability test (CCK8) at 72 hours of PCLX-001 treatment. Optical density (OD) values were normalized to vehicle-treated samples. Error bars, SEM. C, NMT1 immunoblotting on the indicated cells. GAPDH, loading control. D, Relative viability (CCK8) of doxycycline (Dox) treated vs. untreated Tet-inducible NMT1#10 shRNA cells. Blot: NMT1 immunoblotting in cells with or without Dox. GAPDH, loading control. E, Percent change in H460 (KL/K)MUT xenograft tumor volume from mice treated with daily subcutaneous injections of vehicle control or PCLX-001 at dosages of 25 and 50 mg/kg. Treatment was indicated by the colored bars (18 days for the 25 mg/kg group and 10 days for the 50 mg/kg group). **, P = 0.008, one-way ANOVA, Tukey’s multiple comparisons test.