title: Indomethacin induces apoptosis in the EC109 esophageal cancer cell line by releasing second mitochondria-derived activator of caspase and activating caspase-3.
abstract: 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.
authors: Department of Thoracic Surgery, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors: Sida
authors: S
authors: Qin
authors: Department of Thoracic Surgery, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors: Chongwen
authors: C
authors: Xu
authors: Department of Thoracic Surgery, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors: Shuo
authors: S
authors: Li
authors: Department of Oncology, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors: Chengcheng
authors: C
authors: Yang
authors: Department of Thoracic Surgery, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors: Xin
authors: X
authors: Sun
authors: Department of Thoracic Surgery, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors: Xifang
authors: X
authors: Wang
authors: Department of Hematology and Oncology, Georgia Regents University Cancer Center, Augusta, GA 30912, USA.
authors: Shou-Ching
authors: SC
authors: Tang
authors: Department of Thoracic Surgery, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors: Hong
authors: H
authors: Ren
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins; D053148:Caspase 3 / Q000378:metabolism*; D045744:Cell Line, Tumor; D004938:Esophageal Neoplasms / Q000378:metabolism; D006801:Humans; D007213:Indomethacin / Q000633:toxicity*; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D051017:Apoptosis Regulatory Proteins; C412403:DIABLO protein, human; D047908:Intracellular Signaling Peptides and Proteins; D024101:Mitochondrial Proteins; D034741:RNA, Small Interfering; D053148:Caspase 3; D007213:Indomethacin