Document Detail

Closely related colon cancer cell lines display different sensitivity to polyunsaturated fatty acids, accumulate different lipid classes and downregulate sterol regulatory element-binding protein 1.
MedLine Citation:
PMID:  16817902     Owner:  NLM     Status:  MEDLINE    
N-6 polyunsaturated fatty acids (PUFAs) may be associated with increased risk of colon cancer, whereas n-3 PUFAs may have a protective effect. We examined the effects of docosahexaenoic acid (DHA), eicosapentaenoic acid and arachidonic acid on the colon carcinoma cell lines SW480 derived from a primary tumour, and SW620 derived from a metastasis of the same tumour. DHA had the strongest growth-inhibitory effect on both cell lines. SW620 was relatively more growth-inhibited than SW480, but SW620 also had the highest growth rate in the absence of PUFAs. Flow cytometry revealed an increase in the fraction of cells in the G2/M phase of the cell cycle, particularly for SW620 cells. Growth inhibition was apparently not caused by increased lipid peroxidation, reduced glutathione or low activity of glutathione peroxidase. Transmission electron microscopy revealed formation of cytoplasmic lipid droplets after DHA treatment. In SW620 cells an eightfold increase in total cholesteryl esters and a 190-fold increase in DHA-containing cholesteryl esters were observed after DHA treatment. In contrast, SW480 cells accumulated DHA-enriched triglycerides. Arachidonic acid accumulated in a similar manner, whereas the nontoxic oleic acid was mainly incorporated in triglycerides in both cell lines. Interestingly, nuclear sterol regulatory element-binding protein 1 (nSREBP1), recently associated with cell growth regulation, was downregulated after DHA treatment in both cell lines. Our results demonstrate cell-specific mechanisms for the processing and storage of cytotoxic PUFAs in closely related cell lines, and suggest downregulation of nSREBP1 as a possible contributor to the growth inhibitory effect of DHA.
Svanhild A Schønberg; Anne G Lundemo; Torill Fladvad; Kristin Holmgren; Hilde Bremseth; Asbjørn Nilsen; Odrun Gederaas; Kåre E Tvedt; Kjartan W Egeberg; Hans E Krokan
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The FEBS journal     Volume:  273     ISSN:  1742-464X     ISO Abbreviation:  FEBS J.     Publication Date:  2006 Jun 
Date Detail:
Created Date:  2006-07-04     Completed Date:  2006-09-25     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  101229646     Medline TA:  FEBS J     Country:  England    
Other Details:
Languages:  eng     Pagination:  2749-65     Citation Subset:  IM    
Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway.
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MeSH Terms
Cell Cycle
Cell Line, Tumor
Colonic Neoplasms / metabolism*
Docosahexaenoic Acids / metabolism,  pharmacology
Down-Regulation* / drug effects
Eicosanoids / antagonists & inhibitors,  biosynthesis
Enzyme Inhibitors / metabolism,  pharmacology
Fatty Acids, Unsaturated / metabolism,  pharmacology*,  toxicity
Glutathione / metabolism
Lipid Metabolism* / drug effects
Lipid Peroxidation
Oxidants / metabolism,  pharmacology
RNA, Messenger / metabolism
Sterol O-Acyltransferase / antagonists & inhibitors,  metabolism
Sterol Regulatory Element Binding Protein 1 / genetics,  metabolism*
Time Factors
Tumor Cells, Cultured
Vitamin E / metabolism,  pharmacology
Reg. No./Substance:
0/Eicosanoids; 0/Enzyme Inhibitors; 0/Fatty Acids, Unsaturated; 0/Oxidants; 0/RNA, Messenger; 0/Sterol Regulatory Element Binding Protein 1; 1406-18-4/Vitamin E; 25167-62-8/Docosahexaenoic Acids; 70-18-8/Glutathione; EC O-Acyltransferase

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

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