title: Triclosan inhibits enoyl-reductase of type I fatty acid synthase in vitro and is cytotoxic to MCF-7 and SKBr-3 breast cancer cells.
abstract: OBJECTIVE
  Human type I fatty acid synthase has been proposed as a chemotherapeutic target for the treatment of breast cancer based on the inactivation of human beta-ketoacyl synthase activity by cerulenin. Triclosan, a common antibiotic, functions by inhibiting the enoyl-reductase enzymes of type II fatty acid synthases in susceptible bacteria. If triclosan is an inhibitor of human fatty acid synthase and if inhibition of fatty acid synthase is toxic to breast cancer cell lines, triclosan could prove to be a lead compound for the treatment of breast cancer. Consequently, the inhibitory activity of triclosan against vertebrate type I fatty acid synthases and its effects on breast cancer lines in cell culture were investigated.
  
  
  METHODS
  The inhibitory activities of triclosan against human and goose fatty acid synthases and each of the partial reactions were investigated using spectrophotometric assays. The ability of triclosan at various concentrations to inhibit growth and reduce the viability of MCF-7 and SKBr-3 cells in culture was evaluated.
  
  
  RESULTS
  Kinetic studies showed triclosan to be a slow binding inhibitor of human and goose type I fatty acid synthase and to inhibit the partial activity of enoyl-reductase with IC(50) values between 10 and 50 microM. Triclosan at similar concentrations was also shown to inhibit both viability and growth of MCF-7 and SKBr-3 cells in culture.
  
  
  CONCLUSIONS
  The results corroborate the hypothesis that fatty acid synthase may be a target of breast cancer chemotherapy and suggest that inhibitors of the enoyl-reductase partial activity of fatty acid synthase may have chemotherapeutic potential.
authors.affiliation: Department of Biochemistry, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106-4935, USA.
authors.forename: Binqiu
authors.initials: B
authors.lastname: Liu
authors.forename: Yingqiang
authors.initials: Y
authors.lastname: Wang
authors.forename: Kerry L
authors.initials: KL
authors.lastname: Fillgrove
authors.forename: Vernon E
authors.initials: VE
authors.lastname: Anderson
mesh_terms: D000970:Antineoplastic Agents / Q000633:toxicity*; D001943:Breast Neoplasms / Q000473:pathology*; D002470:Cell Survival / Q000187:drug effects*; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH); D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors*; D005260:Female; D006801:Humans; D007700:Kinetics; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D014260:Triclosan / Q000633:toxicity*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D014260:Triclosan; D010088:Oxidoreductases; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH); D064429:Fatty Acid Synthases