Silibinin modulates caudal-type homeobox transcription factor (CDX2), an intestine specific tumor suppressor to abrogate colon cancer in experimental rats.

Abstract

To authenticate the colon cancer preventive potential of silibinin, the efficacy of silibinin needs to be tested by evaluating an organ-specific biomarker. The aim of this study was to evaluate the impact of silibinin on the colonic expression of the caudal-type homeobox transcription factor (CDX2) an intestine specific tumor suppressor gene and its downstream targets in the colon of rats challenged with 1,2 dimethyl hydrazine (DMH). Rats of groups 1 and 2 were treated as control and silibinin control. Rats under groups 3 and 4 were given DMH (20 mg/kg body weight (b.w.) subcutaneously) once a week for 15 consecutive weeks from the 4th week of the experimental period. In addition, group 4 rats alone were treated with silibinin (50 mg/kg b.w. per os) everyday throughout the study period of 32 weeks. Histological investigation and messenger RNA and protein expression studies were performed in the colonic tissues of experimental rats. Findings of the study revealed that DMH administration significantly decreased the expression of CDX2 and Guanylyl cyclase C (GCC) in the colon of experimental rats. Further the decreased levels of CDX2 protein, colonic mucin content, and increased number of mast cells in the colon of DMH alone-administered rats reflects the onset of carcinogenesis. The pathological changes caused due to CDX2 suppression were attenuated by silibinin supplementation.

• Authors: N Sangeetha, N Nalini
• Journal: Human & experimental toxicology (Hum Exp Toxicol) Vol. 34 Issue 1 Pg. 56-64 (Jan 2015) ISSN: 1477-0903 [Electronic] England
• PMID: 24740923 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2014.

Chemical References

• Antineoplastic Agents
• CDX2 Transcription Factor
• Carcinogens
• Cdx2 protein, rat
• Homeodomain Proteins
• RNA, Messenger
• Receptors, Peptide
• Silymarin
• Transcription Factors
• Tumor Suppressor Proteins
• Silybin
• Receptors, Enterotoxin
• Receptors, Guanylate Cyclase-Coupled
• 1,2-Dimethylhydrazine

Topics

• 1,2-Dimethylhydrazine
• Animals
• Antineoplastic Agents (pharmacology, therapeutic use)
• CDX2 Transcription Factor
• Carcinogens
• Colon (drug effects, metabolism, pathology)
• Colonic Neoplasms (chemically induced, drug therapy, metabolism, pathology)
• Homeodomain Proteins (genetics, metabolism)
• Male
• RNA, Messenger (metabolism)
• Rats
• Rats, Wistar
• Receptors, Enterotoxin
• Receptors, Guanylate Cyclase-Coupled (genetics)
• Receptors, Peptide (genetics)
• Silybin
• Silymarin (pharmacology, therapeutic use)
• Transcription Factors (genetics, metabolism)
• Tumor Suppressor Proteins (genetics, metabolism)