Licochalcone-A induces intrinsic and extrinsic apoptosis via ERK1/2 and p38 phosphorylation-mediated TRAIL expression in head and neck squamous carcinoma FaDu cells

• Published in: Food and chemical toxicology 2015-03, Vol.77, p.34-43
• Main Authors: Park, Mi-Ra, Kim, Su-Gwan, Cho, In-A., Oh, Dahye, Kang, Kyeong-Rok, Lee, Sook-Young, Moon, Sung-Min, Cho, Seung Sik, Yoon, Goo, Kim, Chun Sung, Oh, Ji-Su, You, Jae-Seek, Kim, Do Kyung, Seo, Yo-Seob, Im, Hee-Jeong, Kim, Jae-Sung
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Carcinoma, Squamous Cell - genetics; Caspase 3 - genetics; Caspase 3 - metabolism; Caspase 7 - genetics; Caspase 7 - metabolism; Cell Line, Tumor; Cell Survival - drug effects; Chalcones - pharmacology; Chemoprevention; FaDu cells; Glycyrrhiza; Glycyrrhiza - chemistry; Head and Neck Neoplasms - genetics; Humans; Inhibitory Concentration 50; Keratinocytes - drug effects; Keratinocytes - metabolism; Licochalcone-A; Male; Mice; Mice, Nude; Mitogen-Activated Protein Kinase 3 - genetics; Mitogen-Activated Protein Kinase 3 - metabolism; p38 Mitogen-Activated Protein Kinases - genetics; p38 Mitogen-Activated Protein Kinases - metabolism; Pharyngeal squamous carcinoma; Phosphorylation; Plant Extracts - pharmacology; Plant Roots - chemistry; Signal Transduction; Squamous Cell Carcinoma of Head and Neck; TNF-Related Apoptosis-Inducing Ligand - genetics; TNF-Related Apoptosis-Inducing Ligand - metabolism; Xenograft Model Antitumor Assays
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2014.12.013

•Licochalcone-A is cytotoxic, inducing cell death in FaDu cells, but does not affect human normal oral keratinocytes.•Licochalcone-A-induced cell death of FaDu cells is mediated by both extrinsic and intrinsic apoptotic signaling pathways.•Licochalcone-A-induced apoptosis of FaDu cells is triggered by TRAIL expression induced by ERK1/2 and p38 MAPK. We investigated Licochalcone-A (Lico-A)-induced apoptosis and the pathway underlying its activity in a pharyngeal squamous carcinoma FaDu cell line. Lico-A purified from root of Glycyrrhiza inflata had cytotoxic effects, significantly increasing cell death in FaDu cells. Using a cell viability assay, we determined that the IC50 value of Lico-A in FaDu cells was approximately 100 µM. Chromatin condensation was observed in FaDu cells treated with Lico-A for 24 h. Consistent with this finding, the number of apoptotic cells increased in a time-dependent manner when FaDu cells were treated with Lico-A. TRAIL was significantly up-regulated in Lico-A-treated FaDu cells in a dose-dependent manner. Apoptotic factors such as caspases and PARP were subsequently activated in a caspase-dependent manner. In addition, levels of pro-apoptotic factors increased significantly in response to Lico-A treatment, while levels of anti-apoptotic factors decreased. Lico-A-induced TRAIL expression was mediated in part by a MAPK signaling pathway involving ERK1/2 and p38. In xenograft mouse model, Lico-A treatment effectively suppressed the growth of FaDu cell xenografts by activating caspase-3, without affecting the body weight of mice. Taken together, these data suggest that Lico-A has potential chemopreventive effects and should therefore be developed as a chemotherapeutic agent for pharyngeal squamous carcinoma.