Propranolol as a novel adjunctive treatment for head and neck squamous cell carcinoma.

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 gamma-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, Delta Np63 alpha decreased, whereas TAp73 beta 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 gamma-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.