Cholera-toxin suppresses carcinogenesis in a mouse model of inflammation-driven sporadic colon cancer.

Abstract

Human studies and clues from animal models have provided important links between gastrointestinal (GI) tract bacteria and colon cancer. Gut microbiota antigenic stimuli play an important role in shaping the intestinal immune responses. Therefore, especially in the case of inflammation-associated colon cancer, gut bacteria antigens may affect tumorigenesis. The present study aimed to investigate the effects of the oral administration of a bacterial product with known immunomodulatory properties on inflammation-driven colorectal neoplasmatogenesis. For that, we used cholera-toxin and a well-established mouse model of colon cancer in which neoplasia is initiated by a single dose of the genotoxic agent azoxymethane (AOM) and subsequently promoted by inflammation caused by the colitogenic substance dextran sodium sulfate (DSS). We found that a single, low, non-pathogenic dose of CT, given orally at the beginning of each DSS treatment cycle downregulated neutrophils and upregulated regulatory T-cells and IL-10 in the colonic mucosa. The CT-induced disruption of the tumor-promoting character of DSS-induced inflammation led to the reduction of the AOM-initiated colonic polypoidogenesis. This result adds value to the emerging notion that certain GI tract bacteria or their products affect the immune system and render the microenvironment of preneoplastic lesions less favorable for promoting their evolution to cancer.

• Authors: Michael Doulberis, Katerina Angelopoulou, Eleni Kaldrymidou, Anastasia Tsingotjidou, Zaphiris Abas, Suzan E Erdman, Theofilos Poutahidis
• Journal: Carcinogenesis (Carcinogenesis) Vol. 36 Issue 2 Pg. 280-90 (Feb 2015) ISSN: 1460-2180 [Electronic] England
• PMID: 25550315 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected].

Chemical References

• Anticarcinogenic Agents
• IL10 protein, mouse
• Immunologic Factors
• Interleukin-10
• Cholera Toxin

Topics

• Animals
• Anticarcinogenic Agents (pharmacology)
• Carcinogenesis (drug effects)
• Cholera Toxin (pharmacology)
• Colitis (chemically induced)
• Colon (microbiology, pathology)
• Colonic Neoplasms (pathology, prevention & control)
• Immunologic Factors (pharmacology)
• Inflammation (pathology)
• Interleukin-10 (biosynthesis)
• Intestinal Mucosa (microbiology, pathology)
• Male
• Mice
• Mice, Inbred BALB C
• Neoplasms, Experimental (prevention & control)
• Neutrophils (immunology)
• T-Lymphocytes, Regulatory (immunology)