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

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 1,2dimethylhydrazine (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 bcatenin, GSK3b 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 b-catenin and phospho-GSK3b. 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.

Effects of a Potential Probiotic Strain Lactobacillus gasseri ATCC 33323 on Helicobacter pylori-Induced Inflammatory Response and Gene Expression in Coinfected Gastric Epithelial Cells

“…To the best of our knowledge, no study has been conducted to apply the antitumor activity and protective effects of L. gasseri ATCC 33323 on modulating β-catenin expression in gastric epithelial cells stimulated by H. pylori strains. There are only a few reports which used L. rhamnosus (LGG) and L. casei to down-regulate β-catenin expression, thereby preventing the initiation and progression of colon cancer [54,55]. In line with these studies, our results also showed that L. gasseri ATCC 33323 significantly decreased the expression of β-catenin in AGS cells cocultured with clinical H. pylori strains.…”

An Update on the Effects of Probiotics on Gastrointestinal Cancers

“…Ali et al reported that L. casei probiotic supplementation in mice with 1,2dimethylhydrazine-induced colon cancer significantly reduced the number of aberrant crypt foci compared with that in untreated animals. Furthermore, by upregulating the expression of phosphorylated JNK-1, L. casei regulated the expression of β-catenin and phosphorylated GSK3β, leading to significant protective effects against colon cancer (Ali et al, 2019). Sakatani and others have demonstrated that a L. brevis-derived polyphosphate significantly promoted the activation of the ERK signaling pathway, expression of cleaved PARP, and the ratio of cleaved PARP/PARP in SW620 colon cancer cells and mice bearing SW620 tumor xenografts.…”

Structural Characteristics of Inulin and Microcrystalline Cellulose and Their Effect on Ameliorating Colitis and Altering Colonic Microbiota in Dextran Sodium Sulfate-Induced Colitic Mice

“… 3 Inulin, a β-(2–1) linked fructan polymer, can be found in chicory roots, beet roots, leeks, and other natural sources. 13 In addition, as a prebiotic additive in food, inulin has been found to effectively protect mice from developing colon cancer, 14 directly modulate immune responses, and attenuate proinflammatory responses in dendritic cells. 13 Microcrystalline cellulose (MCC, IDF), a novel food additive found in hardwood, softwood, cotton linter, and lignocellulosic materials, especially agricultural residues, 15 can promote the growth of specific flora in the gut and regulate the host microbiota.…”

“… 17 , 18 Inulin and MCC are both plant source fibers that are used as functional additives of yogurt, sausages, DF supplements during pregnancy, and so forth and play an important role in the food and health product industry. 14 In animals, dietary inulin and MCC cannot be hydrolyzed by endogenous enzymes, but they are readily fermented by microbes in the colon and caecum and are beneficial to bifidobacterial growth in the gut. 6 The combined soluble fibers, with high viscosity and fermentability, have been found to attenuate systemic inflammation, promote intestinal microbiota homeostasis, and improve the intestinal morphological integrity of mice suffering from obesity induced by a high-fat diet.…”

“…Microcrystalline cellulose (MCC, IDF), a novel food additive found in hardwood, softwood, cotton linter, and lignocellulosic materials, especially agricultural residues, can promote the growth of specific flora in the gut and regulate the host microbiota . Moreover, MCC has been shown to have positive effects on the gastrointestinal physiology and hypolipidemia, influencing the expression of enzymes involved in lipid metabolism. , Inulin and MCC are both plant source fibers that are used as functional additives of yogurt, sausages, DF supplements during pregnancy, and so forth and play an important role in the food and health product industry . In animals, dietary inulin and MCC cannot be hydrolyzed by endogenous enzymes, but they are readily fermented by microbes in the colon and caecum and are beneficial to bifidobacterial growth in the gut .…”