title: Green tea catechin inhibits fatty acid synthase without stimulating carnitine palmitoyltransferase-1 or inducing weight loss in experimental animals.
abstract: BACKGROUND
  The enzyme fatty acid synthase (FASN) is highly expressed in many human carcinomas and its inhibition is cytotoxic to human cancer cells. The use of FASN inhibitors has been limited until now by anorexia and weight loss, which is associated with the stimulation of fatty acid oxidation.
  
  
  METHODS
  The in vitro effect of (-)-epigallocatechin-3-gallate (EGCG) on fatty acid metabolism enzymes, on apoptosis and on cell signalling was evaluated. In vivo, the effect of EGCG on animal body weight was addressed.
  
  
  RESULTS
  EGCG inhibited FASN activity, induced apoptosis and caused a marked decrease of human epidermal growth factor receptor 2 (HER2), phosphatidylinositol 3-kinase (PI3K)/AKT and extracellular (signal)-regulated kinase (ERK) 1/2 proteins, in breast cancer cells. EGCG did not induce a stimulatory effect on CPT-1 activity in vitro (84% of control), or on animal body weight in vivo (99% of control).
  
  
  CONCLUSIONS
  EGCG is a FASN inhibitor with anticancer activity which does not exhibit cross-activation of fatty acid oxidation and does not induce weight loss, suggesting its potential use as an anticancer drug.
authors.affiliation: Girona Biomedical Research Institute (IdIBGi) and Catalan Institute of Oncology, Dr. Josep Trueta University Hospital, Girona, Spain. mtpuig@iconcologia.es
authors.forename: Teresa
authors.initials: T
authors.lastname: Puig
authors.forename: Joana
authors.initials: J
authors.lastname: Relat
authors.forename: Pedro F
authors.initials: PF
authors.lastname: Marrero
authors.forename: Diego
authors.initials: D
authors.lastname: Haro
authors.forename: Joan
authors.initials: J
authors.lastname: Brunet
authors.forename: Ramon
authors.initials: R
authors.lastname: Colomer
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D015431:Weight Loss / Q000187:drug effects*
chemical_list: D002334:Carnitine O-Palmitoyltransferase; D002392:Catechin; D064429:Fatty Acid Synthases; D018719:Erb-b2 Receptor Tyrosine Kinases; C045651:epigallocatechin gallate