title: Maslinic Acid, a Natural Triterpene, Induces a Death Receptor-Mediated Apoptotic Mechanism in Caco-2 p53-Deficient Colon Adenocarcinoma Cells.
abstract: Maslinic acid (MA) is a natural triterpene present in high concentrations in the waxy skin of olives. We have previously reported that MA induces apoptotic cell death via the mitochondrial apoptotic pathway in HT29 colon cancer cells. Here, we show that MA induces apoptosis in Caco-2 colon cancer cells via the extrinsic apoptotic pathway in a dose-dependent manner. MA triggered a series of effects associated with apoptosis, including the cleavage of caspases -8 and -3, and increased the levels of t-Bid within a few hours of its addition to the culture medium. MA had no effect on the expression of the Bax protein, release of cytochrome-c or on the mitochondrial membrane potential. This suggests that MA triggered the extrinsic apoptotic pathway in this cell type, as opposed to the intrinsic pathway found in the HT29 colon-cancer cell line. Our results suggest that the apoptotic mechanism induced in Caco-2 may be different from that found in HT29 colon-cancer cells, and that in Caco-2 cells MA seems to work independently of p53. Natural antitumoral agents capable of activating both the extrinsic and intrinsic apoptotic pathways could be of great use in treating colon-cancer of whatever origin.
authors.affiliation: Department of Biochemistry and Molecular Biology I, Faculty of Sciences, University of Granada, 18071, Granada, Spain.
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Reyes-Zurita
authors.affiliation: Department of Biochemistry and Molecular Biology I, Faculty of Sciences, University of Granada, 18071, Granada, Spain.
authors.forename: Eva E
authors.initials: EE
authors.lastname: Rufino-Palomares
authors.affiliation: Department of Biochemistry and Molecular Biology I, Faculty of Sciences, University of Granada, 18071, Granada, Spain.
authors.forename: Leticia
authors.initials: L
authors.lastname: García-Salguero
authors.affiliation: Department of Experimental Biology, Biochemistry and Molecular Biology Section. University of Jaen, 23071, Jaén, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Peragón
authors.affiliation: Department of Biochemistry and Molecular Biology I, Faculty of Sciences, University of Granada, 18071, Granada, Spain.
authors.forename: Pedro P
authors.initials: PP
authors.lastname: Medina
authors.affiliation: Department of Organic Chemistry, Section of Natural Products, Faculty of Sciences, University of Granada, 18071, Granada, Spain.
authors.forename: Andrés
authors.initials: A
authors.lastname: Parra
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, 08028, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Cascante
authors.affiliation: Department of Biochemistry and Molecular Biology I, Faculty of Sciences, University of Granada, 18071, Granada, Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: Lupiáñez
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics; D000970:Antineoplastic Agents / Q000737:chemistry; D017209:Apoptosis; D018938:Caco-2 Cells; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics; D045304:Cytochromes c / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D006801:Humans; D020128:Inhibitory Concentration 50; D053078:Membrane Potential, Mitochondrial; D009154:Mutation; D053218:Receptors, Death Domain / Q000378:metabolism*; D016896:Treatment Outcome; D014315:Triterpenes / Q000737:chemistry*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D009828:Oleanolic Acid / Q000031:analogs & derivatives
chemical_list: D000970:Antineoplastic Agents; D053148:Caspase 3; D053181:Caspase 8; D045304:Cytochromes c; D053218:Receptors, Death Domain; D014315:Triterpenes; D016159:Tumor Suppressor Protein p53; C495901:TP53 protein, human; C412811:maslinic acid; D009828:Oleanolic Acid; C505407:CASP3 protein, human; C505530:CASP8 protein, human