Maslinic Acid-Enriched Diet Decreases Intestinal Tumorigenesis in ApcMin/+ 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 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.

Identification of gut‐derived metabolites of maslinic acid, a bioactive compound from Olea europaea L

“…Finally, worth noting that our results indicate that the ingestion of a diet rich in vegetables and legumes as well as olives and olives oil, could provide maslinic acid in sufficient amount as to reach the colon, as has been demonstrated with the administration of a dose as low as 1 mg/kg. The scientific evidence on the beneficial effects of this pentacyclic triterpene, suggest that maslinic acid could exert a chemopreventive activity on colon cancer [1,24,25]. Several studies using HT-29 and Caco-2 cells have evidenced the anti-proliferative and pro-apoptotic activities exerted by this pentacyclic triterpene [1].…”

“…For this reason, and in an effort to elucidate its disposition after its oral administration, we have recently studied its pharmacokinetics through a population approach . The results showed a low oral bioavailability that could be due, in part, to a low intestinal absorption, thus suggesting a higher concentration in the intestinal content where maslinic acid could exert its cancer chemopreventive activities described both in vitro in HT‐29 colon cancer cells and in vivo using a mouse model of intestinal polyposis .…”

“…where maslinic acid could exert its cancer chemopreventive activities described both in vitro in HT-29 colon cancer cells [4] and in vivo using a mouse model of intestinal polyposis [5].…”

Daikenchuto (TU‐100) Suppresses Tumor Development in the Azoxymethane and APCmin/+ Mouse Models of Experimental Colon Cancer

“…A number of agents have been tested and several are implicated to have efficacy in colon cancer prevention including most notably aspirin and sulindac, but also vitamin D and calcium (4–6). A number of natural products have also been investigated including curcumin, ellagiaic acid, polyphenols, isoflavones, and ginsenosides (7–11). …”

Maslinic acid activates mitochondria-dependent apoptotic pathway in cardiac carcinoma

“…MA has been shown to exert anti-tumor activity on some types of cancer [2], including melanoma [3], prostate cancer [4], hepatocellular carcinoma [5] and intestinal cancer [6,7]. Previous studies have demonstrated that MA can induce apoptosis in cancer cells [2,8].…”