title: Effects of the black tea polyphenol theaflavin-2 on apoptotic and inflammatory pathways in vitro and in vivo.
abstract: METHODS
  Theaflavin-2 (TF-2), a major component of black tea extract, induces apoptosis of human colon cancer cells and suppresses serum-induced cyclooxygenase-2 (COX-2) expression 1. Here, we explored the mechanisms for activation of apoptosis, evaluated the impact on inflammatory genes in a broader panel of cells and tested whether topical anti-inflammatory effects could be observed in vivo.
  
  
  RESULTS
  TF-2 triggered apoptosis in five other transformed cancer cell lines, inducing cell shrinkage, membrane blebbing, and mitochondrial clustering within 3 h of treatment. Among a set of pro-apoptotic genes, TF-2 quickly induced the up-regulation of P53 and BAX, suggesting mitochondria as the primary target. Using a cell model for inflammatory response, we showed that TF-2 suppressed the 12-O-tetradecanoylphorbol-13-acetate-induced COX-2 gene expression, and also down-regulated TNF-α, iNOS, ICAM-1, and NFκB. A reporter gene assay showed that TF-2 down-regulated COX-2 at the transcriptional level. We also demonstrated that TF-2 exhibited anti-inflammatory activity in two mouse models of inflammation. Topical application with TF-2 significantly reduced ear edema and produced a pattern of gene down-regulation similar to that observed in the cell model.
  
  
  CONCLUSIONS
  These results suggest that the anti-inflammatory and pro-apoptotic activity of TF-2 may be exploited therapeutically in cancer and other diseases associated with inflammation.
authors.affiliation: WellGen Inc., Commercialization Center for Innovative Technologies, North Brunswick, NJ 08854-8087, USA. agosslau@rutgers.edu
authors.forename: Alexander
authors.initials: A
authors.lastname: Gosslau
authors.forename: David Li
authors.initials: DL
authors.lastname: En Jao
authors.forename: Mou-Tuan
authors.initials: MT
authors.lastname: Huang
authors.forename: Chi-Tan
authors.initials: CT
authors.lastname: Ho
authors.forename: Dave
authors.initials: D
authors.lastname: Evans
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Rawson
authors.forename: Kuang Yu
authors.initials: KY
authors.lastname: Chen
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D044946:Biflavonoids / Q000494:pharmacology / Q000627:therapeutic use*; D002392:Catechin / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D004285:Dogs; D005260:Female; D005419:Flavonoids / Q000494:pharmacology* / Q000627:therapeutic use*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D013662:Tea / Q000737:chemistry*; D014158:Transcription, Genetic / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000972:Antineoplastic Agents, Phytogenic; D044946:Biflavonoids; D005419:Flavonoids; D018836:Inflammation Mediators; D012333:RNA, Messenger; D013662:Tea; D016159:Tumor Suppressor Protein p53; C056068:theaflavin; D002392:Catechin; D051546:Cyclooxygenase 2