Figure 1.

Cell death driven by PT-112 is associated with DAMP emission. (a). Chemical structure of R,R-1,2 cyclohexanediamine-pyrophosphato-platinum(II) (PT-112). (b). IC₅₀ values associated with exposure of 121 human cancer cell lines to PT-112 for 72 hours. Results are means ± SEM, based on cancer cell histology. Mean IC₅₀ ± SEM for all cells is reported in red. **p < .01 (one-way ANOVA), as compared to all other cells confounded. See also Table 1. (c). Residual number of mouse colorectal carcinoma CT26 cells upon exposure to the indicated concentration of PT-112 for 24 or 48 hours. Quantitative results (means ± SEM) are reported. n = 2–3 independent experiments; *p < .05, **p < .01, ***p < .001 (one-way ANOVA), as compared to untreated cells at the same time point. (d). Percentage of DAPI⁺ (dead) mouse mammary carcinoma TSA cells upon exposure to PT-112 in the indicated concentrations for 24 or 48 hours. Representative dotplots (with percentage of events in each quadrant) and quantitative results (means ± SEM) are reported. n = 2–3 independent experiments; *p < .05, **p < .01, ***p < .001 (one-way ANOVA), as compared to untreated cells at the same time point. (e). CALR exposure on PI⁻ TSA cells upon treatment with 50 µg/mL PT-112, 15 µM cisplatin (CDDP), or 2.5 µM mitoxantrone (MTX) for 24 hours. Representative histograms (isotype staining is reported as dashed profile) and quantitative results (mean MFI ± SEM) are reported. n = 2–3 independent experiments; ***p < .001 (one-way ANOVA), as compared to untreated cells. MFI, mean fluorescence intensity. (f,g). ATP (f) and HMGB1 (g) amounts in the supernatant of TSA cells treated as in panel d. Quantitative results (means ± SEM) are reported. n = 2–3 independent experiments; *p < .05, **p < .01, ***p < .001 (one-way ANOVA), as compared to untreated cells.