title: AZD5582, an IAP antagonist that leads to apoptosis in head and neck squamous cell carcinoma cell lines and is eligible for combination with irradiation.
abstract: CONCLUSIONS
  On the one hand, AZD5582, an inhibitor of inhibitor of apoptosis family proteins (IAP), leads to cellular growth arrest and induction of apoptosis in head and neck squamous cell carcinoma (HNSCC) cell lines. On the other hand, it is a viable candidate for combination therapy with irradiation.
  
  
  OBJECTIVE
  The aim and purpose of this study was to evaluate the effects of AZD5582 on HNSCC cell lines.
  
  
  METHODS
  HNSCC cell lines SCC25, Cal27, and FaDu were used for all cell culture experiments. Proliferation assays were used to assess a potential inhibitory effect of AZD5582 and a combination therapy of the IAP inhibitor and irradiation. Colony forming assays were used to determine long-term effects of a combined treatment. Apoptosis was measured via flow cytometry and wound-healing assays were performed.
  
  
  RESULTS
  All three cell lines showed a dose-dependent cytotoxic effect after treatment with AZD5582. It was possible to observe a synergistic and additive effect after short-term treatment of AZD5582 and irradiation in Ca27 and FaDu cells, respectively. All test cell lines showed a significant inhibition of colony formation after combined treatment. Treatment of AZD5582 resulted in apoptosis in SCC25, Cal27, and FaDu cells.
authors.affiliation: a Departments of Otorhinolaryngology, Head and Neck Surgery , Medical University of Vienna , Vienna , Austria.
authors.forename: Lorenz
authors.initials: L
authors.lastname: Kadletz
authors.affiliation: a Departments of Otorhinolaryngology, Head and Neck Surgery , Medical University of Vienna , Vienna , Austria.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Enzenhofer
authors.affiliation: a Departments of Otorhinolaryngology, Head and Neck Surgery , Medical University of Vienna , Vienna , Austria.
authors.forename: Ulana
authors.initials: U
authors.lastname: Kotowski
authors.affiliation: b Radiotherapy , Medical University of Vienna , Vienna , Austria.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Altorjai
authors.affiliation: a Departments of Otorhinolaryngology, Head and Neck Surgery , Medical University of Vienna , Vienna , Austria.
authors.forename: Gregor
authors.initials: G
authors.lastname: Heiduschka
mesh_terms: D000480:Alkynes / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000628:therapy*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D059248:Chemoradiotherapy; D004354:Drug Screening Assays, Antitumor; D006258:Head and Neck Neoplasms / Q000628:therapy*; D006801:Humans; D009842:Oligopeptides / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000480:Alkynes; D000970:Antineoplastic Agents; C586719:N,N'-(2,2'-(hexa-2,4-diyne-1,6-diylbis(oxy))bis(2,3-dihydro-1H-indene-2,1-diyl))bis(1-(2-cyclohexyl-2-(2-(methylamino)propanamido)acetyl)pyrrolidine-2-carboxamide); D009842:Oligopeptides
keywords: AZD5582; Head and neck; IAP; radiotherapy; squamous cell carcinoma