title: Maslinic acid-enriched diet decreases intestinal tumorigenesis in Apc(Min/+) mice through transcriptomic and metabolomic reprogramming.
abstract: Chemoprevention is a pragmatic approach to reduce the risk of colorectal cancer, one of the leading causes of cancer-related death in western countries. In this regard, maslinic acid (MA), a pentacyclic triterpene extracted from wax-like coatings of olives, is known to inhibit proliferation and induce apoptosis in colon cancer cell lines without affecting normal intestinal cells. The present study evaluated the chemopreventive efficacy and associated mechanisms of maslinic acid treatment on spontaneous intestinal tumorigenesis in Apc(Min/+) mice. Twenty-two mice were randomized into 2 groups: control group and MA group, fed with a maslinic acid-supplemented diet for six weeks. MA treatment reduced total intestinal polyp formation by 45% (P<0.01). Putative molecular mechanisms associated with suppressing intestinal polyposis in Apc(Min/+) mice were investigated by comparing microarray expression profiles of MA-treated and control mice and by analyzing the serum metabolic profile using NMR techniques. The different expression phenotype induced by MA suggested that it exerts its chemopreventive action mainly by inhibiting cell-survival signaling and inflammation. These changes eventually induce G1-phase cell cycle arrest and apoptosis. Moreover, the metabolic changes induced by MA treatment were associated with a protective profile against intestinal tumorigenesis. These results show the efficacy and underlying mechanisms of MA against intestinal tumor development in the Apc(Min/+) mice model, suggesting its chemopreventive potential against colorectal cancer.
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Sánchez-Tena
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Reyes-Zurita
authors.forename: Santiago
authors.initials: S
authors.lastname: Díaz-Moralli
authors.forename: Maria Pilar
authors.initials: MP
authors.lastname: Vinardell
authors.forename: Michelle
authors.initials: M
authors.lastname: Reed
authors.forename: Francisco
authors.initials: F
authors.lastname: García-García
authors.forename: Joaquín
authors.initials: J
authors.lastname: Dopazo
authors.forename: José A
authors.initials: JA
authors.lastname: Lupiáñez
authors.forename: Ulrich
authors.initials: U
authors.lastname: Günther
authors.forename: Marta
authors.initials: M
authors.lastname: Cascante
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D019587:Dietary Supplements; D020869:Gene Expression Profiling; D017491:Genes, APC; D007417:Intestinal Polyps / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D046228:Microarray Analysis; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014315:Triterpenes / Q000494:pharmacology*; D009828:Oleanolic Acid / Q000031:analogs & derivatives
chemical_list: D014315:Triterpenes; C412811:maslinic acid; D009828:Oleanolic Acid