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. 2023 Aug 8;14:4758. doi: 10.1038/s41467-023-40518-0

Fig. 1. Prolonged methionine deprivation suppresses ferroptosis in response to cystine deprivation.

Fig. 1

a Representative images show cell death of HT-1080 cells cultured in a medium that is deficient for cystine (Cyss−) or methionine (Met−) or both of them (Cyss−Met−) for 16 h. Dead cells are visualized by PI staining. b, c Cell death (b) or relative lipid ROS (c) in HT-1080 cells treated with cystine or methionine withdrawal or their co-withdrawal for 20 h (b) or 10 h (c). d Cell death of HT-1080 cells cultured in methionine-free medium and treated with erastin (5 μM) for 24 h. e, f Cell death (e) or relative lipid ROS (f) in OS-RC-2 cells treated with cystine withdrawal plus methionine co-withdrawal in the presence of ferrostatin-1 (Fer-1, 10 µM) for 20 h (e) or 8 h (f). g, h Cell death (g) or relative lipid ROS (h) in Hepa1–6 cells treated with cystine withdrawal plus methionine co-withdrawal in the presence of Fer-1 (10 µM) for 24 h (g) or 12 h (h). i, j Cell death (i) or relative lipid ROS ( j) in Hepa1–6 cells treated with IKE (1 µM) plus methionine co-withdrawal for 30 h (i) or 14 h ( j). k–p Effect of prolonged dietary methionine deprivation on IKE-induced tumoral ferroptosis. Experimental design of Hepa1–6 tumor in C57BL/6 mice (k). Tumor-bearing mice were fed with a control (Met+) or methionine-free (Met−) diet and treated with vehicle control, IKE (40 mg/kg), liproxstatin-1 (Lip-1, 10 mg/kg), or their combination. Tumor volume was monitored over time (l, m). MDA contents in isolated tumor tissues were quantified (n). Images of immunohistochemistry for 4HNE in tumor tissue slides were presented; scale bars,100 μm (o). mRNA levels of PTGS2, HMOX1, and TFRC in isolated tumor tissues were quantified (p). n = 3 biological replicates and P values are determined using one-way ANOVA (b–j); n = 9 or 10 mice per group, and data are presented as mean ± s.e.m. and P values are determined using two-way ANOVA (l, m); n = 4 tumors and P values are determined by one-way ANOVA (n, p). Source data are provided as a Source Data file.