title: Propranolol as a novel adjunctive treatment for head and neck squamous cell carcinoma.
abstract: OBJECTIVE
  To investigate propranolol as a novel treatment for head and neck squamous cell carcinoma (HNSCC) in vitro.
  
  
  METHODS
  HNSCC cell lines were cultured and treated with propranolol alone and in combination with cisplatin or γ-irradiation. The alamarBlue assay was performed to assess cell viability, and apoptosis was confirmed via Western immunoblot for cleaved poly-ADP-ribose polymerase (PARP) and caspase-3/7 assays.
  
  
  RESULTS
  Propranolol reduced cell viability and induced apoptosis. In response to propranolol, ΔNp63α decreased, whereas TAp73β and downstream proapoptotic p53 family target genes increased. Expression of the proangiogenic protein vascular endothelial growth factor (VEGF) also decreased. Combination treatment with propranolol and cisplatin resulted in synergistic effects. Propranolol treatment also enhanced the effects of γ-irradiation on cell viability.
  
  
  CONCLUSIONS
  Our results demonstrate that propranolol reduced HNSCC viability, induced apoptosis, and inhibited production of the proangiogenic protein VEGF. These changes may be due to modulation of p53 family proteins, which are critical regulators of chemotherapy-induced apoptosis in HNSCC. Moreover, propranolol is synergistic in combination with cisplatin and reduces HNSCC viability postradiation in vitro, which may have important implications for novel treatments of HNSCC patients.
authors.affiliation: Department of Otolaryngology–Head and Neck Surgery, University of Toronto, Toronto, ON M5G 2N2. nikolaus.wolter@mail.utoronto.ca
authors.forename: Nikolaus E
authors.initials: NE
authors.lastname: Wolter
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Wolter
authors.forename: Danny J
authors.initials: DJ
authors.lastname: Enepekides
authors.forename: Meredith S
authors.initials: MS
authors.lastname: Irwin
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival; D059248:Chemoradiotherapy; D004273:DNA, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D006801:Humans; D011433:Propranolol / Q000627:therapeutic use*; D000077195:Squamous Cell Carcinoma of Head and Neck; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000319:Adrenergic beta-Antagonists; D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53; D011433:Propranolol