Maslinic Acid-Enriched Diet Decreases Intestinal Tumorigenesis in ApcMin/+ Mice through Transcriptomic and Metabolomic Reprogramming Sánchez-Tena, Susana Reyes Zurita, Fernando Jesús Díaz-Moralli, Santiago Vinardell, María Pilar Reed, Michelle García-García, Francisco Dopazo, Joaquín Lupiáñez Cara, José Antonio Günter, Ulrich Cascante Serratosa, Marta Apoptosis Cancer treatment Carcinogenesis Chemoprevention Colorectal cancer Diet Metabolomics Transcriptome analysis 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 ApcMin/+ 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 ApcMin/+ 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 ApcMin/+ mice model, suggesting its chemopreventive potential against colorectal cancer. 2014-03-20T09:02:43Z 2014-03-20T09:02:43Z 2013 info:eu-repo/semantics/article Sánchez-Tena, S.; et al. Maslinic Acid-Enriched Diet Decreases Intestinal Tumorigenesis in ApcMin/+ Mice through Transcriptomic and Metabolomic Reprogramming. Plos One, 8(3): e59392 (2013). [http://hdl.handle.net/10481/30993] 1932-6203 doi: 10.1371/journal.pone.0059392 http://hdl.handle.net/10481/30993 eng info:eu-repo/grantAgreement/EC/FP7/22263 http://creativecommons.org/licenses/by-nc-nd/3.0/ info:eu-repo/semantics/openAccess Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License Public Library of Science (PLOS)