title: Inhibitory effect of linoleic acid on transformation of IEC6 intestinal cells by in vitro azoxymethane treatment.
abstract: 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.affiliation: Department of Molecular Pathology, Nara Medical University School of Medicine, Kashihara, Japan.
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Sasaki
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yoshida
authors.forename: Hideo
authors.initials: H
authors.lastname: Shimura
authors.forename: Masayosi
authors.initials: M
authors.lastname: Ichiba
authors.forename: Tomonori
authors.initials: T
authors.lastname: Sasahira
authors.forename: Takasumi
authors.initials: T
authors.lastname: Shimomoto
authors.forename: Ayumi
authors.initials: A
authors.lastname: Denda
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kuniyasu
mesh_terms: D000818:Animals; D001093:Arachidonate 15-Lipoxygenase / Q000235:genetics / Q000378:metabolism; D001397:Azoxymethane / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D004249:DNA Damage; D066246:ErbB Receptors / Q000378:metabolism; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000473:pathology; D008024:Ligands; D019787:Linoleic Acid / Q000494:pharmacology*; D016859:Lipoxygenase Inhibitors; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D002273:Carcinogens; D008024:Ligands; D016859:Lipoxygenase Inhibitors; D020319:Oligodeoxyribonucleotides, Antisense; D047495:PPAR gamma; D051028:bcl-2-Associated X Protein; D019787:Linoleic Acid; D001093:Arachidonate 15-Lipoxygenase; D019392:Cytochrome P-450 CYP2E1; D051546:Cyclooxygenase 2; D066246:ErbB Receptors; D001397:Azoxymethane