Figure 5 from N-Myristoytransferase Inhibition Causes Mitochondrial Iron Overload and Parthanatos in TIM17A-Dependent Aggressive Lung Carcinoma

NMTi treatment activates the DNA damage response and sensitizes (KL/K)MUT lung carcinoma cells to platinum doublet chemotherapy. A, Phospho-H2A.X staining in (KL/K)MUT H460 lung cancer cells treated with 1 μmol/L PCLX-001 (NMTi) or vehicle control for 72 hours. Graph: percentage of p-H2A.X positive cells calculated from at least 400 cells per condition. Crossbar, group mean; error bars, SEM. ***, P < 0.0002 (Student t test). Representative images are shown. Arrowheads, nuclei containing p-H2A.X-positive foci. Bar, 25 μm. B, Phospho-H2A.X staining of H460 xenograft tumor sections from mice treated with 25 mg/kg PCLX-001 or vehicle control. Square, area magnified for each on the right. Arrowhead, nuclei with p-H2A.X positive foci. Bar, 100, 30, and 10 μm in the left, middle, and right columns, respectively. C, Viability test (CCK8) of (KL/K)MUT HCC44 and H1792 cells treated with PCLX-001 (NMTi) in combination with platinum-based chemotherapy. Left, Dose–response of cisplatin in combination with NMTi (50 nmol/L). Middle, Dose–response of pemetrexed in combination with NMTi (50 nmol/L). Right, Dose–response of cisplatin in combination with a single dose of pemetrexed (5 μmol/L) and a single dose of NMTi (125 nmol/L). OD was normalized to vehicle-treated samples. One representative experiment from two independent experiments with the same result is shown. Error bars, SEM. **, P < 0.0001; *, P < 0.0025, two-way ANOVA with the interaction between drug and dose level. All P values are adjusted for multiple testing using the Šídák method.