title: Differential cell growth/apoptosis behavior of 13-hydroxyoctadecadienoic acid enantiomers in a colorectal cancer cell line.
abstract: Cyclooxygenases (COXs) and lipoxygenases (LOXs) are important enzymes that metabolize arachidonic and linoleic acids. Various metabolites generated by the arachidonic acid cascade regulate cell proliferation, apoptosis, differentiation, and senescence. Hydroxyoctadecadienoic acids (HODEs) are synthesized from linoleic acid, giving two enantiomeric forms for each metabolite. The aim was to investigate the effect of 13-HODE enantiomers on nondifferentiated Caco-2 cell growth/apoptosis. Our results indicate that 13(S)-HODE decreases cell growth and DNA synthesis of nondifferentiated Caco-2 cells cultured with 10% fetal bovine serum (FBS). Moreover, 13(S)-HODE showed an apoptotic effect that was reduced in the presence of a specific peroxisome proliferator-activated receptor-γ (PPARγ) antagonist. In addition, we observed that 13(S)-HODE but not 13(R)-HODE is a ligand to PPARγ, confirming the implication of this nuclear receptor in 13(S)-HODE actions. In contrast, 13(R)-HODE increases cell growth and DNA synthesis in the absence of FBS. 13(R)-HODE interaction with BLT receptors activates ERK and CREB signaling pathways, as well as PGE2 synthesis. These results suggest that the proliferative effect of 13(R)-HODE could be due, at least in part, to COX pathway activation. Thus both enantiomers use different receptors and have contrary effects. We also found these differential effects of 9-HODE enantiomers on cell growth/apoptosis. Therefore, the balance between (R)-HODEs and (S)-HODEs in the intestinal epithelium could be important to its cell growth/apoptosis homeostasis.
authors.affiliation: Departament de Fisiologia, Facultat de Farmàcia, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Marisol
authors.initials: M
authors.lastname: Cabral
authors.affiliation: Departament de Fisiologia, Facultat de Farmàcia, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Martín-Venegas
authors.affiliation: Departament de Fisiologia, Facultat de Farmàcia, Universitat de Barcelona, Barcelona, Spain jjmoreno@ub.edu.
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Moreno
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D018938:Caco-2 Cells; D049109:Cell Proliferation / Q000187:drug effects*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004261:DNA Replication / Q000187:drug effects; D015232:Dinoprostone / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007536:Isomerism; D008024:Ligands; D008041:Linoleic Acids / Q000737:chemistry / Q000494:pharmacology*; D047495:PPAR gamma / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D008024:Ligands; D008041:Linoleic Acids; D047495:PPAR gamma; C024348:13-hydroxy-9,11-octadecadienoic acid; D048049:Extracellular Signal-Regulated MAP Kinases; D015232:Dinoprostone
keywords: PPARγ; apoptosis; cell growth; cyclooxygenase; lipoxygenase