Disulfidptosis-related molecular features in clinically actionable genes and drug response associated with disulfidptosis in vitro. (A) Disulfidptosis scores for 25 types of cancer that including 760 cancer cell lines. Cancer types are sorted by the median disulfidptosis score (horizontal black line) for each cancer type. Each dot represents one cancer cell line. Sample sizes for each cancer type are listed near the bottom. The horizontal black dotted line means the median value of disulfidptosis score in all the 760 cancer cell lines that divide all the cancer cell lines into disulfidptosis score-high (red) and disulfidptosis score-low (green) groups. (B–C) Relative cell viability in the HeLa, Huh-7 (B; Green label; Disulfidptosis-score low), A375 and SK-MEL-28 (C; Red label; Disulfidptosis-score high) cells cultured in glucose-containing (+Glucose) or glucose-free (-Glucose) medium with or without indicated concentrations of liproxstatin-1 (Lip-1), Z-VAD-FMK (Z-VAD), necrostatin-1s (Nec-1s), chloroquine (CQ), and dithiothreitol (DTT) for about 16 h. (D) LDH release analysis of SK-MEL-28 cells after indicated treatments for about 14 h. (E) Representative EdU staining images and the ratio of EdU positive SK-MEL-28 cells after indicated treatments for about 12 h. The nuclei were stained with Hoechst (blue). Scale bar, 50 μm (200 × ). (F) Cell cycle distribution of SK-MEL-28 cells after indicated treatments for about 12 h. (G) Apoptosis analysis of SK-MEL-28 cells by flow cytometry at 14 h after receiving indicted treatments and stained by PI and Annexin V. (H) Caspase-3 activity of SK-MEL-28 cells after indicated treatments for about 14 h. STS, staurosporine, the apoptosis inducer. (I) Drug response associated with the disulfidptosis status in SKCM. The green point denotes drug sensitivity; the magenta point denotes drug resistance. (J–K) Dose-response curves for relative cell viability of etoposide, methotrexate, CMK (E; drug sensitivity), GW-441756, ABT-263, and NS-87877 (F; drug resistant) in glucose-containing (+Glucose) and glucose-free (-Glucose) conditions in the SK-MEL-28 cells. Quantification data are presented as mean ± SD and compared with one-way ANOVA in B–H and two-way ANOVA in J-K. NS, not significant; *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)