Inhibitory effect of a standardized pomegranate fruit extract on Wnt signalling in 1, 2-dimethylhydrazine induced rat colon carcinogenesis.

Abstract

BACKGROUND:

De-regulation of Wnt signalling is increasingly being implicated in both experimental and human carcinogenesis including colon cancer.

AIMS:

Our goal was to identify possible dietary agents that block Wnt signalling as a step toward investigating new strategies for suppression of colon cancer. Pomegranate extract has emerged as an intriguing candidate due to its polyphenolic content.

METHODS:

We used a 1,2-dimethylhydrazine dihydrochloride (DMH)-induced rat colon carcinogenesis model to investigate the expression pattern of the main key players in Wnt signalling by reverse transcription polymerase chain reaction (RT-PCR) analysis.

RESULTS:

Our results showed that many Wnt-target genes, e.g., Wnt5a, frizzled receptor (FRZ)-8, β-catenin, T cell factor/lymphoid enhancer binding protein (Tcf4/Lef1), c-myc and cyclin D1, were up-regulated whereas adenomatous polyposis coli (APC) and axin1 exhibited down-regulation in colonic tissues of our DMH-colon cancer group compared with the normal group. Standardized pomegranate extract minimised all the aberrant alterations observed in the studied Wnt genes in colonic tissues of the DMH+pomegranate group as compared with the DMH-induced colon cancer group. This effect was also confirmed by the normalization of survival rate, inhibition of tumour incidence and a reduction of serum tumour marker carcinoembryonic antigen (CEA) level. Histopathological observations provided supportive evidence for the biochemical and molecular analyses.

CONCLUSIONS:

Standardized pomegranate extract holds great promise in the field of colon cancer prevention by dietary agents.

• Authors: Nermin Abdel Hamid Sadik, Olfat Gamil Shaker
• Journal: Digestive diseases and sciences (Dig Dis Sci) Vol. 58 Issue 9 Pg. 2507-17 (Sep 2013) ISSN: 1573-2568 [Electronic] United States
• PMID: 23722564 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Carcinogens
• Plant Extracts
• Wnt Proteins
• 1,2-Dimethylhydrazine

Topics

• 1,2-Dimethylhydrazine
• Adenocarcinoma (chemically induced, metabolism, pathology, prevention & control)
• Animals
• Antineoplastic Agents, Phytogenic (analysis)
• Carcinogens
• Colon (pathology)
• Colonic Neoplasms (chemically induced, metabolism, pathology, prevention & control)
• Disease Models, Animal
• Fruit (chemistry)
• Lythraceae (chemistry)
• Male
• Phytotherapy
• Plant Extracts (therapeutic use)
• Rats
• Rats, Wistar
• Wnt Proteins (metabolism)