Phenformin Induces Caspase-dependent Apoptosis of FaDu Head and Neck Squamous Cell Carcinoma Cells

Background/Aim: The present study aimed to investigate the apoptotic effects of phenformin, a therapeutic agent for diabetes, on head and neck squamous cell carcinoma (HNSCC). Materials and Methods: Cytotoxicity was measured by the MTT and live/dead cell assay. Phenformin-induced apoptotic FaDu cell death and its associated cellular signaling pathways were investigated by hematoxylin and eosin staining, 4',6-diamidino-2-phenylindole staining, caspase-3 activity assay, fluorescence-activated cell sorting analysis, and western blotting. Results: Phenformin promoted death of and apoptotic processes in FaDu cells, including morphological alterations and nuclear condensation. Furthermore, treatment with phenformin increased caspase-3 activity and apoptotic populations via the caspase cascade through cleavage of capspase-8, -9, and -3 and poly(ADP-ribose) polymerase in FaDu cells. Moreover, phosphorylation levels of mitogen-activated protein kinases, nuclear factor-kappa B, and AKT were downregulated in FaDu cells by phenformin. Conclusion: Phenformin induced death of FaDu cells via caspasedependent extrinsic and intrinsic apoptosis pathways and is a promising novel therapeutic agent for HNSCC.