Faculty Collaboration Database

Black raspberries suppress colonic adenoma development in ApcMin/+ mice: relation to metabolite profiles. Carcinogenesis 2015 Oct;36(10):1245-53

Date

08/08/2015

Pubmed ID

26246425

Pubmed Central ID

PMC4598815

DOI

10.1093/carcin/bgv117

Scopus ID

2-s2.0-84943804507 (requires institutional sign-in at Scopus site)   40 Citations

Abstract

Freeze-dried black raspberries (BRBs) have demonstrated chemopreventive effects in a dietary intervention trial with human colorectal cancer patients. The aim of this study was to investigate BRB-caused metabolite changes using the Apc(Min/+) mouse as a model of human colorectal cancer. Wild-type (WT) mice were fed control diet, and Apc(Min/+) mice were fed either control diet or control diet supplemented with 5% BRBs for 8 weeks. Colonic and intestinal polyp size and number were measured. A non-targeted metabolomic analysis was conducted on colonic mucosa, liver and fecal specimens. Eight weeks of BRB treatment significantly decreased intestinal and colonic polyp number and size in Apc(Min/+) mice. The apc gene mutation significantly changed 52 metabolites in colonic mucosa associated with increased amino acid and decreased lipid metabolites, as well as 39 liver and 8 fecal metabolites. BRBs significantly reversed 23 apc-regulated metabolites, including 13 colonic mucosa, 8 liver and 2 fecal metabolites that were involved in amino acid, glutathione, lipid and nucleotide metabolism. Of these, changes in eight metabolites were linearly correlated with decreased colonic polyp number and size in BRB-treated Apc(Min/+) mice. Elevated levels of putrescine and linolenate in Apc(Min/+) mice were significantly decreased by BRBs. Ornithine decarboxylase expression, the key enzyme in putrescine generation, was fully suppressed by BRBs. These results suggest that BRBs produced beneficial effects against colonic adenoma development in Apc(Min/+) mice and modulated multiple metabolic pathways. The metabolite changes produced by BRBs might potentially reflect the BRB-mediated chemopreventive effects in colorectal cancer patients.

Author List

Pan P, Skaer CW, Wang HT, Stirdivant SM, Young MR, Oshima K, Stoner GD, Lechner JF, Huang YW, Wang LS

MESH terms used to index this publication - Major topics in bold

Adenoma
Adenomatous Polyposis Coli Protein
Animals
Colorectal Neoplasms
Disease Models, Animal
Fruit
Gene Expression Regulation, Neoplastic
Humans
Intestinal Mucosa
Mice
Mice, Transgenic
Putrescine
Rubus
alpha-Linolenic Acid