FIGURE 5.

Treatment with ER stress inducers enhanced ricin toxicity in A549 cells. (A) A549 cells treated with Tm (500 ng/ml) for 2 h followed by a 4 h Tm +ricin co‐treatment significantly enhanced ricin‐induced cell death (AUC of 30,830 ±1609 vs. 33,962 ±1236 of ricin‐only). (B) Treatment with DTT (5 mM) for 2 h prior to a 4 h ricin exposure significantly enhanced ricin‐induced cell death (AUC of 27,082 ±3935 vs. 41,420 ±2200 of ricin‐only) (C) Treatment with Tg (10 nM) for 2 h followed by a 4 h Tg +ricin co‐treatment significantly enhanced ricin‐induced cell death (AUC of 20,541 ±1344 vs. 23,326 ±769 of ricin‐only). Closed symbols, ricin‐only; open symbols, dual treatment, error bars represent the 95% CI. The green line and dots represent the mean and 95% CI of control cell viability; orange line and dots represent the mean and 95% CI of cell viability for the indicated ER stress‐inducing compound. Tm and DTT treatment exhibited independent toxicity, which was corrected for in the combinatorial treatment curves. Experiments were independently repeated in triplicate with six to 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 S8