Licochalcone-A induces intrinsic and extrinsic apoptosis via ERK1/2 and p38 phosphorylation-mediated TRAIL expression in head and neck squamous carcinoma FaDu cells. (March 2015)

• Record Type: Journal Article
• 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
• Is Part Of: Food and chemical toxicology. Volume 77(2015)
• Page Start: 34
• Page End: 43
• Publication Date: 2015-03
• Subjects: Lico-A Licochalcone-A -- HNSCC head and neck squamous cell carcinoma -- TRAIL TNF-related apoptosis-inducing ligand -- PARP poly ADP-ribose polymerase -- FasL Fas ligand -- FADD Fas-associated protein with death domain -- BID BH3 interacting-domain death agonist -- Bcl-2 B-cell lymphoma 2 -- Bcl-xL B-cell lymphoma-extra large -- Bax Bcl-2-associated X protein -- BAD Bcl-2-associated death promoter -- NHOK normal human oral keratinocytes -- FBS fetal bovine serum -- MTT 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide -- DAPI 4′-6-diamidino-2-phenylinodole -- PI propodium iodide -- MAPK mitogen activated protein kinase -- DR death receptor; Pharyngeal squamous carcinoma -- Licochalcone-A -- FaDu cells -- Apoptosis -- Chemoprevention; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2014.12.013
• Languages: English
• ISSNs: 0278-6915

Abstract

Graphical Abstract: Highlights: 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. Abstract: 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.