Indomethacin induces apoptosis in the EC109 esophageal cancer cell line by releasing second mitochondria-derived activator of caspase and activating caspase-3

The use of non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with a reduced risk of various types of cancer, including esophageal cancer. However, the mechanisms underlying the antineoplastic effects of NSAIDs in esophageal cancer remain to be elucidated. In the present study, a significant inhibition in cell viability was observed in the EC109 cells following treatment with different concentrations of indomethacin, and these effects occurred in a dose- and time-dependent manner. This inhibition was due to the release of second mitochondria-derived activator of caspase (Smac) into the cytosol and the activation of caspase-3. Subsequently, flow cytometry was performed to investigate indomethacin-induced apoptosis following the overexpression or knockdown of Smac, and western blot analysis was performed to determine the expression of Smac and the activation of caspase-3. Overexpression of Smac was promoted apoptosis, while downregulation of Smac significantly inhibited apoptosis. Western blot analysis demonstrated that indomethacin induced apoptosis through releasing Smac into the cytosol and activating caspase-3. These results indicated that Smac is essential for the apoptosis induced by indomethacin in esophageal cancer cells.