FIGURE 4.

External induction of ER stress further sensitizes dTHP‐1 cells to ricin‐induced death. (A) dTHP‐1 cells treated with Tm (175 ng/ml) for 2 h followed by 2 h Tm +ricin resulted in significantly enhanced ricin‐induced cell death (AUC of 554.5 ±76.5 vs. 1504 ±103 of ricin‐only). (B) Treatment with DTT (2.5 mM) for 2 h followed by a 2 h ricin exposure significantly enhanced ricin‐induced cell death (AUC of 709.1 ±70.1 vs. 1677 ±73 of ricin‐only). (C) Treatment with varying concentrations of Tg for 2 h followed by a 2 h co‐treatment with ricin and Tg. Tg significantly increased ricin‐induced cell death at all concentrations but the two lowest concentrations tested (p ≤ 0.0014) without independent toxicity. Tm and DTT treatment exhibited significant independent toxicity, which was corrected for in the dual‐treatment curves. Closed symbols, ricin‐only; open symbols, dual treatment, error bars represent the 95% confidence interval (CI). Green line and dots represent the mean and 95% CI of control; orange line and dots represent the mean and 95% CI of the indicated ER stress‐inducing compound; red line and dots represent the mean and 95% CI of ricin treatment. Experiments were independently repeated in triplicate with eight replicate wells per treatment condition, with controls for independent effects included in each trial. Representative survival curves are shown. Graphical representation of the unnormalized data and results of pairwise statistical testing for treatment interactions are available in Figure S7