Modulation of JNK-1/ β-catenin signaling by: Lactobacillus casei, inulin and their combination in 1,2-dimethylhydrazine-induced colon cancer in mice

Bibliographic Information
Authors: Ali M.S.; Hussein R.M.; Gaber Y.; Hammam O.A.; Kandeil M.A.
Journal: RSC Advances
Publisher: Royal Society of Chemistry
Publication Date: 2019
Volume / Issue: Volume 9 / Issue 50
Pages: 29368–29383
ISSN: 20462069
DOI: 10.1039/c9ra04388h
Scopus: View on Scopus
Document Type: Article
Access: All Open Access; Gold Open Access; Green Open Access
Authors and Affiliations
Ali M.S., Department of Biochemistry, Faculty of Pharmacy, Beni-Suef University, Salah Salem Street, Beni-Suef, 62514, Egypt; Hussein R.M., Department of Biochemistry, Faculty of Pharmacy, Beni-Suef University, Salah Salem Street, Beni-Suef, 62514, Egypt, Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, Mutah University, Al-Karak, 61710, Jordan; Gaber Y., Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, Mutah University, Al-Karak, 61710, Jordan, Department of Microbiology and Immunology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, 62514, Egypt; Hammam O.A., Pathology Department, Theodor Bilharz Research Institute, Giza, 12411, Egypt; Kandeil M.A., Department of Biochemistry, Faculty of Veterinary Medicine, Beni-Suef University, Egypt
Abstract
Colon cancer is a complex disease that involves numerous genetic alterations that change the normal colonic mucosa into invasive adenocarcinoma. In the current study, the protective effects of inulin (prebiotic), Lactobacillus casei (L. casei, probiotic) and their combination (synbiotic) on 1,2-dimethylhydrazine (DMH)-induced colon cancer in male Swiss mice were evaluated. Animals were divided into: Control group, DMH-treated group, DMH plus inulin, DMH plus L. casei and DMH plus inulin plus L. casei-treated groups. Fecal microbiome analysis, biochemical measurements, histopathological examination of the colon tissues, immunostaining and Western blotting analysis of β-catenin, GSK3β and JNK-1 were performed. The prebiotic-, probiotic- and synbiotic-treated groups showed decreased levels of carcinoembryonic antigen and a lower number of aberrant crypt foci compared to the DMH-treated group with the synbiotic group exhibiting a superior effect. Furthermore, all treatments showed a body weight-reducing effect. Administration of inulin, L. casei or their combination increased the expression level of phospho-JNK-1 while they decreased the expression level of β-catenin and phospho-GSK3β. Remarkably, L. casei treatment resulted in enrichment of certain beneficial bacterial genera i.e. Akkermansia and Turicibacter. Therefore, administration of L. casei and inulin as a synbiotic combination protects against colon cancer in mice. © The Royal Society of Chemistry 2019.
Keywords
Diseases; Mammals; Probiotics; 1 ,2-dimethylhydrazine; Carcinoembryonic antigen; Catenin signaling; Expression levels; Genetic alterations; Histopathological examinations; Lactobacillus casei; Protective effects; Polysaccharides
Citation Information
Scopus Citations: 40
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