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

Year: 2024
Type: other
Abstract: 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.
Language: English
Field: Medicine
Open Access status: gold
OpenAlex ID: W4400980293
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