Maslinic Acid-Enriched Diet Decreases Intestinal Tumorigenesis in ApcMin/+ Mice through Transcriptomic and Metabolomic Reprogramming
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AutorSánchez-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
Public Library of Science (PLOS)
ApoptosisCancer treatmentCarcinogenesisChemopreventionColorectal cancerDietMetabolomicsTranscriptome analysis
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]
PatrocinadorFinancial support was provided by grant SAF2011-25726 and personal financial support (FPU program) from the Spanish government and also from the Red Temática de Investigación Cooperativa en Cáncer, Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation & European Regional Development Fund “Una manera de hacer Europa” (ISCIII-RTICC grants RD06/0020/004 and RD06/0020/1019 and BIO2011-27069, MICINN). The authors have also received financial support from the AGAUR-Generalitat de Catalunya (grant 2009SGR1308, 2009 CTP 00026 and Icrea Academia Award 2010 granted to M.C.) and the European Commission (FP7) ETHERPATHS KBBE-grant agreement no. 22263. The authors thank the Bio-NMR EU project (Contract # 261863) for providing NMR access to the HWB-NMR facility. Finally, the authors are grateful for the financial support from Biomaslinic S.L. (Granada, Spain).
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.