title: Licochalcone-A induces intrinsic and extrinsic apoptosis via ERK1/2 and p38 phosphorylation-mediated TRAIL expression in head and neck squamous carcinoma FaDu cells.
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.
authors.affiliation: Oral Biology Research Institute, Chosun University, Gwangju 501-759, Republic of Korea; Department of Biomedical Science, CHA University, Seongnam, Gyeongghi-do 487-101, Republic of Korea.
authors.forename: Mi-Ra
authors.initials: MR
authors.lastname: Park
authors.affiliation: Oral Biology Research Institute, Chosun University, Gwangju 501-759, Republic of Korea; Regional Innovation Center for Dental Science and Engineering, Chosun University, Gwangju 501-759, Republic of Korea.
authors.forename: Su-Gwan
authors.initials: SG
authors.lastname: Kim
authors.affiliation: Oral Biology Research Institute, Chosun University, Gwangju 501-759, Republic of Korea; Regional Innovation Center for Dental Science and Engineering, Chosun University, Gwangju 501-759, Republic of Korea.
authors.forename: In-A
authors.initials: IA
authors.lastname: Cho
authors.affiliation: Oral Biology Research Institute, Chosun University, Gwangju 501-759, Republic of Korea; Regional Innovation Center for Dental Science and Engineering, Chosun University, Gwangju 501-759, Republic of Korea.
authors.forename: Dahye
authors.initials: D
authors.lastname: Oh
authors.affiliation: Oral Biology Research Institute, Chosun University, Gwangju 501-759, Republic of Korea; Regional Innovation Center for Dental Science and Engineering, Chosun University, Gwangju 501-759, Republic of Korea.
authors.forename: Kyeong-Rok
authors.initials: KR
authors.lastname: Kang
authors.affiliation: Oral Biology Research Institute, Chosun University, Gwangju 501-759, Republic of Korea; Regional Innovation Center for Dental Science and Engineering, Chosun University, Gwangju 501-759, Republic of Korea.
authors.forename: Sook-Young
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Oral Biology Research Institute, Chosun University, Gwangju 501-759, Republic of Korea.
authors.forename: Sung-Min
authors.initials: SM
authors.lastname: Moon
authors.affiliation: Department of Pharmacy, College of Pharmacy, Mokpo National University, Muan, Jeonnam 353-729, Republic of Korea.
authors.forename: Seung Sik
authors.initials: SS
authors.lastname: Cho
authors.affiliation: Department of Pharmacy, College of Pharmacy, Mokpo National University, Muan, Jeonnam 353-729, Republic of Korea.
authors.forename: Goo
authors.initials: G
authors.lastname: Yoon
authors.affiliation: Oral Biology Research Institute, Chosun University, Gwangju 501-759, Republic of Korea.
authors.forename: Chun Sung
authors.initials: CS
authors.lastname: Kim
authors.affiliation: Oral Biology Research Institute, Chosun University, Gwangju 501-759, Republic of Korea; Regional Innovation Center for Dental Science and Engineering, Chosun University, Gwangju 501-759, Republic of Korea.
authors.forename: Ji-Su
authors.initials: JS
authors.lastname: Oh
authors.affiliation: Oral Biology Research Institute, Chosun University, Gwangju 501-759, Republic of Korea.
authors.forename: Jae-Seek
authors.initials: JS
authors.lastname: You
authors.affiliation: Oral Biology Research Institute, Chosun University, Gwangju 501-759, Republic of Korea; Regional Innovation Center for Dental Science and Engineering, Chosun University, Gwangju 501-759, Republic of Korea.
authors.forename: Do Kyung
authors.initials: DK
authors.lastname: Kim
authors.affiliation: Oral Biology Research Institute, Chosun University, Gwangju 501-759, Republic of Korea.
authors.forename: Yo-Seob
authors.initials: YS
authors.lastname: Seo
authors.affiliation: Department of Biochemistry, Rush University Medical Center, Chicago, IL 60612, USA.
authors.forename: Hee-Jeong
authors.initials: HJ
authors.lastname: Im
authors.affiliation: The Division of Natural Medical Sciences, College of Health Science, Chosun University, Gwangju 501-759, Republic of Korea. Electronic address: js_kim@chosun.ac.kr.
authors.forename: Jae-Sung
authors.initials: JS
authors.lastname: Kim
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053179:Caspase 7 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D047188:Chalcones / Q000494:pharmacology*; D018890:Chemoprevention; D006035:Glycyrrhiza / Q000737:chemistry; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D020128:Inhibitory Concentration 50; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology; D018517:Plant Roots / Q000737:chemistry; D015398:Signal Transduction; D000077195:Squamous Cell Carcinoma of Head and Neck; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D047188:Chalcones; D010936:Plant Extracts; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; C505409:Casp3 protein, mouse; C505524:Casp7 protein, mouse; D053148:Caspase 3; D053179:Caspase 7; C070840:licochalcone A
keywords: Apoptosis; Chemoprevention; FaDu cells; Licochalcone-A; Pharyngeal squamous carcinoma