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Metabonomic Variation of Exopolysaccharide from Rhizopus nigricans on AOM/DSS-Induced Colorectal Cancer in Mice

Authors Lu Y, Wang J, Ji Y, Chen K

Received 8 August 2019

Accepted for publication 4 November 2019

Published 20 November 2019 Volume 2019:12 Pages 10023—10033

DOI https://doi.org/10.2147/OTT.S226451

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Ms Shreya Arora

Peer reviewer comments 2

Editor who approved publication: Dr Leo Jen-Liang Su


Yan Lu,1 Jiayue Wang,1 Yueshan Ji,1 Kaoshan Chen1–3

1School of Life Science, Shandong University, Qingdao 266000, People’s Republic of China; 2National Glycoengineering Research Center, Shandong University, Qingdao 266000, People’s Republic of China; 3Anhui Provincial Engineering Research Center for Polysaccharide Drugs, Anhui Province Key Laboratory of Active Biological Macromolecules, Drug Research & Development Center, School of Pharmacy, Wannan Medical College, Wuhu 241002, People’s Republic of China

Correspondence: Kaoshan Chen
School of Life Science and National Glycoengineering Research Center, Shandong University, No. 72 Binhai Road, Qingdao 266000, People’s Republic of China
Tel/Fax +86 532 5863 0858
Email ksc313@126.com

Background: Colorectal cancer (CRC), which occurs at the junction of the rectum and sigmoid colon, is a common malignancy associated with poor prognosis and high mortality worldwide. The exopolysaccharide (EPS1-1), isolated from the fermentation broth of Rhizopus nigricans (R. nigricans), has been reported to possess anti-CRC properties. However, the metabolic alterations caused by azoxymethane (AOM) and dextran sulfate sodium (DSS) are still unknown.
Methods: In the present study, a mice colon cancer model was established by treatment with AOM/DSS. LC-MS/MS-based metabolomics studies were performed to analyze metabolic alterations at the tissue level. Partial least squares discriminant analysis (PLS-DA) was used to identify differentially expressed metabolites.
Results: Nineteen distinct metabolites were identified that were associated with disruptions in the following pathways: biosynthesis of unsaturated fatty acids, pyrimidine metabolism, phenylalanine metabolism, fatty acid metabolism, folate biosynthesis, and inositol phosphate metabolism. Furthermore, six significantly altered metabolites were involved in these six pathways. Compared with the Model group, the expression of cytosine, deoxyuridine, 20-hydroxy-leukotriene E4, and L-homocysteic acid was lower, whereas that of 2-dehydro-3-deoxy-6-phospho-D-gluconic acid and hematoporphyrin was higher in the EPS1-1 group.
Conclusion: The results of multivariate statistical analysis demonstrate a promising application of the above metabolites by EPS1-1 in CRC therapy. Deeper understanding of the related mechanism warrants further investigation.

Keywords: exopolysaccharide, Rhizopus nigricans, metabolomics, colorectal cancer, azoxymethane/dextran sulfate sodium, LC-MS/MS

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