Project description: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.
2017-02-09 | MTBLS240 | MetaboLights
Project description:Global studies of microbial diversity in Apc Min/+ mice treated with atorvastatin
| PRJNA831634 | ENA
Project description:Intestinal microbiome of APC min/+ mice treated with black soybean seed coat extract
| PRJNA1182577 | ENA
Project description:RNA seq of Campylobacter jejuni infected Apc Min/+ mice
Project description:This experiment reports the RNA microarray data from the microarray analysis performed to the RNA isolated from colonic mucosal layer of Apc Min/+ mice. Apc Min/+ mice develop polyps in both the small and large intestine, with a greater incidence of intestinal adenomas observed in the former. We wanted to evaluate if maslinic acid (MA), a natural pentacyclic triterpene widely present in dietary plants and in olive fruit skins, could prevent spontaneous intestinal tumorigenesis in Apc Min/+ mice and through with mechanism MA executes its function. To do so, Apc Min/+ mice were fed for 6 weeks with a standard diet (control animals) or with the same diet supplemented with 100 mg of MA/kg feed (MA-treated animals). After 6 weeks, animals were killed and large intestine of each dead mouse was removed and placed on a plastic plate that was kept at 4ºC. After removal of the rectum, the colon was opened longitudinally with fine scissors, and mucus and feces were washed away. The colonic mucosal layer was incubated in Trizol for 3 min and scraped off of the muscle layer with the edge of a sterile glass slide. Cells were transferred into 800 microL trizol. Total RNA was isolated by using the Trizol method according to the manufacturer's protocol. Subsequently, it was purified by using the RNeasy Mini kit and digesting it with DNase I (Qiagen) according to the manufacturer's protocol. RNA pellets were resuspended in DEPC-treated, RNase-free water, and their purity and quantity were determined spectrophotometrically by using the NanoDrop ND-1000. RNA samples were considered suitable for further processing if their absorbance ratio 260/280 was higher than 1.9. Integrity was tested by using lab-on-a-chip technology on the BioAnalyzer 2100.
Project description:Western diet enhances intestinal tumorigenesis in Min/+ mice, associating with mucosal metabolic and inflammatory stress and loss of Apc heterozygosity We investigated the interaction of WD and heterozygous mutation in the Apc gene in the histologically normal intestinal mucosa of ApcMin/+ (Min/+) mice. AIN-93G diet vs. a diet modified from AIN-93G, with high fat and low fiber, vitamin D, calcium and folate. (66.4% of total fat from milk, and 33.6% from rapeseed and sunflower oil)
Project description:We report sustained changes in the chromatin accessibility landscape of adipose tissue macrophages (ATMs) from high fat diet (HFD)-fed mice persist long after return to regular diet (RD). We compared the data of ATAC-seq performed on nuclei extracted from FACS-sorted ATMs isolated from HFD, RD-RD and HFD-RD-fed mice. Inter-group comparisons revealed the highest diversity and hence the greatest number of differentially accessible regions (DARs) to occur between ATMs from RD-RD and HFD-RD-fed mice, and considerably fewer DARs were identified between ATMs from HFD-RD vs HFD-fed mice. Association of DARs with the nearest gene and gene ontology (GO) enrichment analysis revealed considerable pathway enrichment, especially pathways coding for angiogenesis and inflammatory response, in HFD-RD group when compared to RD-RD group. The results altogether indicated that most changes in chromatin landscape induced by HFD-feeding are maintained as open chromatin positions for a long time, suggesting that HFD-feeding leads to long-term reprograming of ATMs and renders them prone to pro-angiogenic and pro-inflammatory responses.