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Inhibitory Effect of a Standardized Pomegranate Fruit Extract on Wnt Signalling in 1, 2-Dimethylhydrazine Induced Rat Colon Carcinogenesis

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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.

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Abbreviations

APC:

Adenomatous polyposis coli

AOM:

Azoxymethane

CK2:

Casein kinase2

CEA:

Carcinoembryonic antigen

DMH:

1,2-dimethylhydrazine

EA:

Ellagic acid

FRZ:

Frizzled receptors

GAEs:

Gallic acid equivalents

GSK3β:

Glycogen synthase kinase 3β

JNKs:

c-Jun N-terminal kinase

PKCa:

Protein kinase Ca

RT-PCR:

Reverse transcription polymerase chain reaction

Tcf/Lef:

T cell factor/lymphoid enhancer binding protein

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Acknowledgments

The authors acknowledge Dr Osama Helmy, Pathology Department, National Cancer Institute, Cairo University, Cairo, Egypt for performing the histopathological examinations of this study. The present work was supported by the financial assistance provided by Faculty of Pharmacy, Cairo University, Cairo, Egypt.

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  1. Biochemistry Department, Faculty of Pharmacy, Cairo University, Kasr El-Eini Street, Cairo, 11562, Egypt

    Nermin Abdel Hamid Sadik

  2. Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Cairo, Egypt

    Olfat Gamil Shaker

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Correspondence to Nermin Abdel Hamid Sadik.

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Sadik, N.A.H., Shaker, O.G. Inhibitory Effect of a Standardized Pomegranate Fruit Extract on Wnt Signalling in 1, 2-Dimethylhydrazine Induced Rat Colon Carcinogenesis. Dig Dis Sci 58, 2507–2517 (2013). https://doi.org/10.1007/s10620-013-2704-z

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