Yo-Seob Seo1, Tae-Hyeon Kim2, Hyangi Lim2, Ji-Su Oh3, Jae-Seek You3, Gyeong-Je Lee4, Sun-Kyoung Yu2, DO Kyung Kim2, Heung-Joong Kim2, Chun Sung Kim2, Sook-Young Lee5, Su-Gwan Kim3, Jae-Sung Kim6. 1. Department of Oral and Maxillofacial Radiology, Chosun University, Gwang-Ju, Republic of Korea. 2. Oral Biology Research Institute, Chosun University, Gwang-Ju, Republic of Korea. 3. Department of Oral and Maxillofacial Surgery, Chosun University, Gwang-Ju, Republic of Korea. 4. Department of Prosthodontics, School of Dentistry, Chosun University, Gwang-Ju, Republic of Korea. 5. Marine Bio Research Center, Chosun University, Wando-gun, Republic of Korea. 6. Oral Biology Research Institute, Chosun University, Gwang-Ju, Republic of Korea js_kim@chosun.ac.kr.
Abstract
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-κB, and AKT were down-regulated in FaDu cells by phenformin. CONCLUSION: Phenformin induced death of FaDu cells via caspase-dependent extrinsic and intrinsic apoptosis pathways and is a promising novel therapeutic agent for HNSCC. Copyright
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-κB, and AKT were down-regulated in FaDu cells by phenformin. CONCLUSION:Phenformin induced death of FaDu cells via caspase-dependent extrinsic and intrinsic apoptosis pathways and is a promising novel therapeutic agent for HNSCC. Copyright
Authors: Varun Monga; Benjamin J Miller; Munir Tanas; Sarag Boukhar; Bryan Allen; Carryn Anderson; Laura Stephens; Stacey Hartwig; Steven Varga; Jon Houtman; Lei Wang; Weizhou Zhang; Omar Jaber; Jon Thomason; David Kuehn; Maheen Rajput; Catherine Metz; K D Zamba; Sarah Mott; Chinemerem Abanonu; Sudershan Bhatia; Mohammed Milhem Journal: J Immunother Cancer Date: 2021-07 Impact factor: 13.751