Document Detail


Inhibitory effect of linoleic acid on transformation of IEC6 intestinal cells by in vitro azoxymethane treatment.
MedLine Citation:
PMID:  16094650     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The effect of linoleic acid (LA) on growth and transformation of IEC6 intestinal cells was examined. IEC6 cells expressed mRNAs of 15-lipooxygenase (LOX15) and peroxisome proliferator-activated receptor (PPAR)gamma but not COX-2. Cell growth was suppressed by LA in a dose-dependent manner in IEC6 cells. Three-week treatment with LA provided IEC6 cells a quiescent state. LA-induced growth inhibition was abrogated by exposure to antisense S-oligodeoxynucleotides (S-ODNs) for LOX15 and/or PPARgamma. In an in vitro carcinogenesis model, IEC6 cells, which had confirmed CYP2E1 expression and activity, were continuously treated with AOM and/or LA for 40 weeks. DNA injury in AOM-treated cells was suppressed to the control level by concurrent LA treatment. Colony formation of AOM-treated cells in soft agar was suppressed by treatment with LA, which was reversed by exposure to antisense S-ODNs for LOX15 and/or PPARgamma. AOM-treated IEC6 cells formed s.c. tumors in 9 of 12 mice, whereas AOM+LA-treated cells formed no tumor. IEC6 cells showed no remarkable alteration of protein production by AOM treatment, whereas cells treated with AOM+LA showed decreased epidermal growth factor receptor (EGFR) and phospho-EGFR and increased BAX. These findings suggest that LA inhibited AOM-induced transformation of COX-2-negative IEC6 cells, which was possibly mediated with PPARgamma ligands generated by LOX15 from LA.
Authors:
Takamitsu Sasaki; Kazuhiro Yoshida; Hideo Shimura; Masayosi Ichiba; Tomonori Sasahira; Takasumi Shimomoto; Ayumi Denda; Hiroki Kuniyasu
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  118     ISSN:  0020-7136     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2006 Feb 
Date Detail:
Created Date:  2005-12-05     Completed Date:  2006-02-07     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  593-9     Citation Subset:  IM    
Copyright Information:
Copyright 2005 Wiley-Liss, Inc.
Affiliation:
Department of Molecular Pathology, Nara Medical University School of Medicine, Kashihara, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Arachidonate 15-Lipoxygenase / antagonists & inhibitors,  genetics,  metabolism
Azoxymethane / toxicity*
Carcinogens / toxicity*
Cell Transformation, Neoplastic / drug effects*
Cyclooxygenase 2 / metabolism
Cytochrome P-450 CYP2E1 / metabolism
DNA Damage
Intestinal Mucosa / drug effects*,  pathology
Ligands
Linoleic Acid / pharmacology*
Mice
Mice, Inbred BALB C
Neoplasms, Experimental / chemically induced,  pathology,  prevention & control*
Oligodeoxyribonucleotides, Antisense / pharmacology
PPAR gamma / antagonists & inhibitors,  genetics,  metabolism
Phosphorylation
Rats
Receptor, Epidermal Growth Factor / metabolism
bcl-2-Associated X Protein / metabolism
Chemical
Reg. No./Substance:
0/Carcinogens; 0/Ligands; 0/Oligodeoxyribonucleotides, Antisense; 0/PPAR gamma; 0/bcl-2-Associated X Protein; 2197-37-7/Linoleic Acid; 25843-45-2/Azoxymethane; EC 1.13.11.33/Arachidonate 15-Lipoxygenase; EC 1.14.14.1/Cytochrome P-450 CYP2E1; EC 1.14.99.1/Cyclooxygenase 2; EC 2.7.10.1/Receptor, Epidermal Growth Factor

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