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

• Published in: Anticancer research 2019-07, Vol.39 (7), p.3499-3506
• Main Authors: Seo, Yo-Seob, Kim, Tae-Hyeon, Lim, Hyangi, Oh, Ji-Su, You, Jae-Seek, Lee, Gyeong-Je, Yu, Sun-Kyoung, Kim, DO Kyung, Kim, Heung-Joong, Kim, Chun Sung, Lee, Sook-Young, Kim, Su-Gwan, Kim, Jae-Sung
• Format: Article
• Language: English
• Subjects: 4',6-Diamidino-2-phenylindole; Adenosine diphosphate; AKT protein; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Caspase; Caspase 3 - metabolism; Caspase 7 - metabolism; Caspase-3; Cell death; Cell Line, Tumor; Cell Survival - drug effects; Chemical compounds; Cytotoxicity; Diabetes mellitus; Fas Ligand Protein - metabolism; Flow cytometry; Fluorescence; Head & neck cancer; Head and Neck Neoplasms - drug therapy; Humans; Kinases; Measurement methods; Mortality; Pharmacology; Phenformin - pharmacology; Phosphorylation; Poly(ADP-ribose); Poly(ADP-ribose) polymerase; Ribose; Squamous cell carcinoma; Squamous Cell Carcinoma of Head and Neck - drug therapy; Staining; Toxicity; Western blotting
• ISSN: 0250-7005; 1791-7530
• DOI: 10.21873/anticanres.13496

The present study aimed to investigate the apoptotic effects of phenformin, a therapeutic agent for diabetes, on head and neck squamous cell carcinoma (HNSCC). 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. 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-κB, and AKT were down-regulated in FaDu cells by phenformin. Phenformin induced death of FaDu cells via caspase-dependent extrinsic and intrinsic apoptosis pathways and is a promising novel therapeutic agent for HNSCC.