Figure 6. cAMP inducers sensitize cancer cells to CAD-induced cytotoxicity.

(A) Cell death of MCF7 cells treated with indicated concentrations of siramesine or ebastine and forskolin for 48 h.

(B) Cell death of MCF7 cells treated with indicated concentrations of siramesine and IBMX for 48 h.

(C) Representative confocal images of MCF7 cells treated as indicated for 16 h and stained for galectin-3 and LAMP2. See Fig. S5B for LAMP2 and merged LAMP2 and galectin-3 stainings. Scale bar, 10 μm.

(D) Flamindo2 geometric mean fluorescence intensities (geo-MFIs; left) and cell death (right) of MCF7-Flamindo2 cells treated with non-targeting control (NTC) or CXCR4 siRNAs for 72 h. For cell death measurements, cells were treated with DMSO or indicated concentrations of siramesine for the last 48 h.

(E and F) Cell death of MCF7 cells treated with indicated combinations of indicated CADs and DPIC (E) or salmeterol (F) for 48 h.

(G) Kinetics of Flamindo2 geo-MFIs in MCF7-Flamindo2 cells treated as indicated for 0-20 min in the absence of extracellular Ca²⁺ (left) and representative flow cytometry profiles after 20 min treatment (right).

Error bars, SD of ≥ 3 independent experiments. * P < 0.05, ** P < 0.01, **** P < 0.0001 as analyzed by 2-tailed, homoscedastic student’s t-test.