Protective Effect of Lactobacillus casei on DMH-Induced Colon Carcinogenesis in Mice

Abstract

The administration of probiotics is a promising approach to reduce the prevalence of colon cancer, a multifactorial disease, with hereditary factors, as well as environmental lifestyle-related risk factors. Biogenic polyamines, putrescine, spermidine, and spermine are small cationic molecules with great roles in cell proliferation and differentiation as well as regulation of gene expression. Ornithine decarboxylase is the first rate-limiting enzyme for polyamine synthesis, and upregulation of ornithine decarboxylase activity and polyamine metabolism has been associated with abnormal cell proliferation. This paper is focused on studying the protective role of Lactobacillus casei ATCC 393 in a chemically induced mouse model of colon carcinogenesis, directing our attention on aberrant crypt foci as preneoplastic markers, and on polyamine metabolism as a possible key player in carcinogenesis. BALB/c mice were administered 1,2-dimethylhydrazine dihydrochloride (DMH) to induce colon cancer (20 mg/kg body weight, subcutaneous, twice a week for 24 weeks). L. casei ATCC 393 was given orally (10 CFU, twice a week), 2 weeks before DMH administration. Hematoxylin and eosin staining, high-performance liquid chromatography, and Western blotting were used to evaluate aberrant crypt foci, urinary polyamines, and ornithine decarboxylase expression in the colon. The experimental data showed that the preventive administration of L. casei ATCC 393 may delay the onset of cancer as it significantly reduced the number of DMH-induced aberrant crypt foci, the levels of putrescine, and the expression of ornithine decarboxylase. Hence, this probiotic strain has a prospective role in protection against colon carcinogenesis, and its antimutagenic activity may be associated with the maintenance of polyamine metabolism.

Pretreatment with probiotic Bifico ameliorates colitis‐associated cancer in mice: Transcriptome and gut flora profiling

“…We also detected a tremendous expansion of the genus Lactobacillus , a member of the Bifico bacterial group. As reported by numerous studies, treatment with various strains of Lactobacillus reduces the severity of colitis and colitis‐associated carcinogenesis in both mice and humans Therefore, we assume that Lactobacillus is the crucial component in Bifico's chemoprevention of colitis‐associated tumorigenesis. Nevertheless, we did not detect any significant alteration in abundance of Bifidobacteria or Enterococcus , 2 other components in the Bifico cocktail, probably because we tested mucosa tissues rather than stool specimens, and the vast majority of the bacteria was excreted with feces.…”

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

“…76 In addition, our results agree with the data obtained by Irecta-Nájera et al, 2017, as they showed in their study the protective effect of L. casei on DMH-treated mice. 78 Previous studies reported on the benecial effect of Turicibacter enrichment in the gut. Turicibacter has been correlated to the production of butyric acid, a short chain fatty acid, that act as an immunomodulators.…”

Modulation of Anti-Tumour Immune Responses by Probiotic Bacteria

“…Lenoir et al [ 96 ] reported that, in C57BL/6 mice treated with DMH and Lactobacillus casei BL23, the secretion of cytokines was altered in response to probiotic administration and balanced Th17 responses emerged, culminating in the reduction of tumour incidence. L. casei ATCC 393 also delayed the onset of cancer, reduced the number of aberrant crypt foci [ 97 ], and modified pro-inflammatory cytokine levels in serum and T cell populations in the spleen [ 98 ] in DMH-induced colon carcinogenesis in mice. In addition, in a mouse model of azoxymethane (AOM) carcinogenesis, L. acidophilus reduced colonic lesions by 57%, and increased serum levels of IFN-γ and IL-10, as well as the number of circulating CD4+ and CD8+ T cells [ 99 ].…”