| Fatty acid synthesis is a therapeutic target in human liposarcoma. | |
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MedLine Citation:
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PMID: 20372807 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Liposarcomas (LS) are mesenchymal tumors that can recur after surgical resection and often do not respond to presently available medical therapies. This study demonstrates the dependence of LS on de novo long-chain fatty acid synthesis for growth. Lipogenesis can be impaired by inhibiting the activities of lipogenic enzymes, including acetyl CoA-carboxylase (ACC) and fatty acid synthase (FASN), or by suppressing the expression of key genes involved in the pathway and its regulation. The FASN inhibitors cerulenin and orlistat reduced the growth of two LS cell lines (LiSa2, SW872), as did inhibition of ACC with soraphen A. CDDO-Me, a synthetic triterpenoid, suppressed expression of Spot 14 and FASN genes and likewise inhibited LS cell growth. Importantly, the anti-proliferative effect of each agent was prevented by the co-administration of palmitate, the major product of cellular long-chain fatty acid synthesis. In stark contrast to LS cells, these compounds had no effect on the growth of fibroblasts. Four biochemically distinct agents that target critical points in the fatty acid synthetic pathway exert anti-proliferative effects on LS cells, and rescue of cell growth by palmitic acid suggests that reduced tumor cell lipogenesis mediates the growth inhibition. These findings warrant further studies aimed at the clinical exploitation of the dependence of LS cell growth on fatty acids. |
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Authors:
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Arne M Olsen; Burton L Eisenberg; Nancy B Kuemmerle; Alison J Flanagan; Peter M Morganelli; Portia S Lombardo; Johannes V Swinnen; William B Kinlaw |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: International journal of oncology Volume: 36 ISSN: 1791-2423 ISO Abbreviation: Int. J. Oncol. Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-04-07 Completed Date: 2010-11-22 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9306042 Medline TA: Int J Oncol Country: Greece |
Other Details:
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Languages: eng Pagination: 1309-14 Citation Subset: IM |
Affiliation:
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Department of Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acetyl-CoA Carboxylase
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metabolism Cell Line, Tumor Cell Proliferation Dose-Response Relationship, Drug Fatty Acid Synthetase Complex / metabolism Fatty Acids / chemistry* Fibroblasts / metabolism Gene Expression Regulation, Neoplastic* Humans Lactones / pharmacology Lipids / chemistry Liposarcoma / metabolism* Reverse Transcriptase Polymerase Chain Reaction |
| Grant Support | |
ID/Acronym/Agency:
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DK07508/DK/NIDDK NIH HHS; R01CA126618/CA/NCI NIH HHS; //Howard Hughes Medical Institute |
| Chemical | |
Reg. No./Substance:
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0/Fatty Acids; 0/Lactones; 0/Lipids; 96829-58-2/orlistat; EC 6.-/Fatty Acid Synthetase Complex; EC 6.4.1.2/Acetyl-CoA Carboxylase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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