Document Detail


Triclosan inhibits enoyl-reductase of type I fatty acid synthase in vitro and is cytotoxic to MCF-7 and SKBr-3 breast cancer cells.
MedLine Citation:
PMID:  11935210     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND AND PURPOSE: 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:
Binqiu Liu; Yingqiang Wang; Kerry L Fillgrove; Vernon E Anderson
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.     Date:  2002-01-09
Journal Detail:
Title:  Cancer chemotherapy and pharmacology     Volume:  49     ISSN:  0344-5704     ISO Abbreviation:  Cancer Chemother. Pharmacol.     Publication Date:  2002 Mar 
Date Detail:
Created Date:  2002-04-05     Completed Date:  2002-05-09     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7806519     Medline TA:  Cancer Chemother Pharmacol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  187-93     Citation Subset:  IM    
Affiliation:
Department of Biochemistry, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106-4935, USA.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / toxicity*
Breast Neoplasms / pathology*
Cell Survival / drug effects*
Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)
Fatty Acid Synthetase Complex / antagonists & inhibitors*
Female
Humans
Kinetics
Oxidoreductases / antagonists & inhibitors*
Triclosan / toxicity*
Tumor Cells, Cultured
Grant Support
ID/Acronym/Agency:
DK 07319/DK/NIDDK NIH HHS; GM-36562/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 3380-34-5/Triclosan; EC 1.-/Oxidoreductases; EC 1.3.1.9/Enoyl-(Acyl-Carrier-Protein) Reductase (NADH); EC 6.-/Fatty Acid Synthetase Complex

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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