title: The Role of cIAP1 and XIAP in Apoptosis Induced by Tumor Necrosis Factor Alpha in Esophageal Squamous Cell Carcinoma Cells.
abstract: The inhibitor of apoptosis protein (IAP) family are reported to play important roles in cancer cells evading apoptosis. However, the significance of their expression in human esophageal squamous cell carcinoma (ESCC) cells remains uncertain.
  
  
  
  The present study aimed to investigate the role of the IAP family members in tumor necrosis factor-α (TNF-α)-induced apoptosis of human ESCC cells.
  
  
  
  Five human ESCC cell lines were pretreated with TNF-α, cycloheximide (CHX, protein synthesis inhibitor), epoxomicin (proteasome inhibitor). Apoptosis assay and protein study with Western blot testing were conducted. Knockdown experiments with IAP siRNA were conducted, and the effect on cell apoptosis was analyzed.
  
  
  
  Significant apoptosis was induced in five ESCC cell lines by TNF-α plus CHX stimulation, but not when treated with TNF-α or CHX alone. The protein expression levels of cIAP1 and XIAP were decreased by treatment with TNF-α in the presence of CHX, and the degree of cIAP1 and XIAP expression decrease was correlated with sensitivity to TNF-α plus CHX-induced apoptosis. Epoxomicin suppressed TNF-α plus CHX-induced degradation of survivin, cIAP1, and XIAP, in addition to apoptosis. A caspase inhibitor (z-VAD-fmk) suppressed TNF-α plus CHX-induced apoptosis, but did not suppress degradation of survivin, cIAP1, and XIAP. Furthermore, cIAP1 or XIAP siRNA transfected cells underwent apoptosis in response to treatment with TNF-α alone. Double knockdown of both genes resulted in further increased apoptosis.
  
  
  
  cIAP1 and XIAP play an essential role in the resistance of ESCC cells against apoptosis.
authors.affiliation: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Hikami
authors.affiliation: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan. shiozaki@koto.kpu-m.ac.jp.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shiozaki
authors.affiliation: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Kitagawa-Juge
authors.affiliation: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ichikawa
authors.affiliation: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kosuga
authors.affiliation: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Konishi
authors.affiliation: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Komatsu
authors.affiliation: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Fujiwara
authors.affiliation: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Kazuma
authors.initials: K
authors.lastname: Okamoto
authors.affiliation: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Eigo
authors.initials: E
authors.lastname: Otsuji
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D003513:Cycloheximide / Q000494:pharmacology*; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques / Q000379:methods; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D061988:Proteasome Inhibitors / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D034622:RNA Interference / Q000187:drug effects / Q000502:physiology; D013223:Statistics as Topic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism*
chemical_list: D051034:Inhibitor of Apoptosis Proteins; D009842:Oligopeptides; D061988:Proteasome Inhibitors; D011500:Protein Synthesis Inhibitors; D014409:Tumor Necrosis Factor-alpha; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D003513:Cycloheximide; C494833:BIRC2 protein, human; D044767:Ubiquitin-Protein Ligases; C078846:epoxomicin
keywords: Apoptosis; Cycloheximide; Esophageal cancer; IAP; TNF-α