High physiological concentrations of artificial sweeteners decreased the viability and increase apoptosis of Caco2 cells through the sweet taste receptor (T1R3). (a) Caco-2 cell viability was measured using the Cell Counting Kit-8 (CCK8) assay following 24 h exposure to the artificial sweeteners sucralose, saccharin, and aspartame at concentrations ranging from 0.01 to 10,000 µM. Absorbance was normalized to a 0 µM control and expressed as percentage viability. n = 8. (b,c) Caco-2 cell viability was measured as for (a) following the siRNA knockdown of T1R3 for 24 h and exposure to sucralose, saccharin, and aspartame (10 mM) for a further 24 h. A representative blot of T1R3 and load control actin were shown to confirm siRNA knockdown using 50 µg of protein (b). Caco-2 cells were collected following exposure to sucralose, saccharin, and aspartame at concentrations ranging from 0.1 to 1000 µM for 24 h and analyzed by flow cytometry. Cell death (d) and apoptosis (e) were measured as propidium iodide and annexin V-positive and annexin V-positive cells, respectively. n = 5–6. Data are expressed as mean ± S.E.M. * p < 0.05 versus vehicle (0 µM).