(A) Rates of MDCK cell death (left Y-axis, blue) correspond with cell extrusion rates (right Y-axis, yellow) in response to UV-C when treated with extrusion inhibitors. (B) Representative images of apoptotic cells with and without compounds that block extrusion. When extrusion occurs, the dying cell DNA lies above (out of plane from) the neighboring cells with a contracted actin ring but when it fails, it lies in the same plane as surrounding cells with an uncontracted actin ring. Only the S1P2 antagonist JTE013 causes significant S1P accumulation in the dying cell (second column), whereas blocking extrusion with the other compounds does not impact S1P levels, where p values of each drug treatment compared to control are listed on each S1P panel as asterisks (n = 4). Bar = 10 µm. (C) Ratio of reduction of extrusion to reduction of apoptosis shows nearly a 1:1 correlation throughout, where p-values compared to S1P2 are not significant. (D) Compounds used to block extrusion do not affect apoptosis rates in single MDCK cells treated with EGTA in response to UV. (E) Quantification of UV-induced apoptotic NIH 3T3 cells in the presence of vehicle or JTE-013; All results are expressed as mean values ± STD of three separate experiments (*p < 0.01, **p < 0.005, ***p < 0.005, and ****p < 0.0001), and NS in graphs B, D, and E indicate that p values of a unpaired T-test are not significant.