| Inhibitory effect of linoleic acid on transformation of IEC6 intestinal cells by in vitro azoxymethane treatment. | |
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MedLine Citation:
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PMID: 16094650 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Takamitsu Sasaki; Kazuhiro Yoshida; Hideo Shimura; Masayosi Ichiba; Tomonori Sasahira; Takasumi Shimomoto; Ayumi Denda; Hiroki Kuniyasu |
Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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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:
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Created Date: 2005-12-05 Completed Date: 2006-02-07 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 0042124 Medline TA: Int J Cancer Country: United States |
Other Details:
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Languages: eng Pagination: 593-9 Citation Subset: IM |
Copyright Information:
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Copyright 2005 Wiley-Liss, Inc. |
Affiliation:
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Department of Molecular Pathology, Nara Medical University School of Medicine, Kashihara, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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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