title: Anti-cancer effect of (-)-epigallocatechin-3-gallate (EGCG) in head and neck cancer through repression of transactivation and enhanced degradation of β-catenin.
abstract: OBJECTIVE
  Aberrant expression of β-catenin is highly associated with progression of various cancers including head and neck cancer (HNC). Green tea is most commonly used beverage in the world and one of the more bioactive compounds is the antioxidant epigallocatechin gallate (EGCG). This study was performed to investigate the mechanism by which EGCG inhibits the growth of HNC, focusing on the modulation of the expression and activity of β-catenin.
  
  
  METHODS
  In vitro effects of EGCG on the transcription, translation, or degradation of β-catenin were investigated. Antitumor effects of EGCG in vivo were evaluated in a syngeneic mouse model and β-catenin expression was checked in HNC patients' samples.
  
  
  RESULTS
  β-catenin expression was elevated in tumor samples of HNC patients. EGCG induced apoptosis in KB and FaDu cells through the suppression of β-catenin signaling. Knockdown of β-catenin using siRNA enhanced the proapoptotic activities of EGCG. EGCG decreased mRNA and transcriptional activity of β-catenin in p53 wild-type KB cells. EGCG also enhanced the ubiquitination and proteasomal degradation of β-catenin. The suppression of β-catenin and consequent apoptosis were observed in response to EGCG treatment in a syngeneic mouse model. In conclusion, we report that EGCG inhibits β-catenin expression through multiple mechanisms including decreased transcription and increased ubiquitin-mediated 26S proteasomal degradation.
  
  
  CONCLUSIONS
  This study proposes a novel molecular rationale for antitumor activities of green tea in HNCs.
authors.affiliation: Department of Otolaryngology, School of Medicine; Department of Molecular Science & Technology, Ajou University, Suwon, Korea.
authors.forename: Yoo Seob
authors.initials: YS
authors.lastname: Shin
authors.affiliation: Department of Otolaryngology, School of Medicine; Department of Molecular Science & Technology, Ajou University, Suwon, Korea.
authors.forename: Sung Un
authors.initials: SU
authors.lastname: Kang
authors.affiliation: Department of Otolaryngology, School of Medicine; Department of Molecular Science & Technology, Ajou University, Suwon, Korea.
authors.forename: Ju Kyeong
authors.initials: JK
authors.lastname: Park
authors.affiliation: Department of Otolaryngology, School of Medicine; Department of Molecular Science & Technology, Ajou University, Suwon, Korea.
authors.forename: Yang Eun
authors.initials: YE
authors.lastname: Kim
authors.affiliation: Department of Otolaryngology, School of Medicine.
authors.forename: Yeon Soo
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville.
authors.forename: Seung Joon
authors.initials: SJ
authors.lastname: Baek
authors.affiliation: Department of Nutrition and Food Science, College of Agriculture and Natural Resources, University of Maryland, College Park, USA.
authors.forename: Seong-Ho
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Otolaryngology, School of Medicine; Department of Molecular Science & Technology, Ajou University, Suwon, Korea. Electronic address: ostium@ajou.ac.kr.
authors.forename: Chul-Ho
authors.initials: CH
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D055785:Gene Knockdown Techniques; D016158:Genes, p53 / Q000187:drug effects; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008875:Middle Aged; D009368:Neoplasm Transplantation; D015398:Signal Transduction / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects*; D064570:Ubiquitin-Specific Proteases / Q000235:genetics; D051176:beta Catenin / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051176:beta Catenin; D002392:Catechin; C045651:epigallocatechin gallate; D064570:Ubiquitin-Specific Proteases
keywords: (-)-epigallocatechin-3 gallate; Head and cancer; P53; Transactivation; Ubiquitination; β-catenin