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Published on: October 27, 2015
Inhibitory effect of a standardized pomegranate fruit extract on Wnt signalling in 1, 2-dimethylhydrazine induced rat
Nermin Abdel Hamid Sadik1, Olfat Gamil Shaker
1Biochemistry Department, Faculty of Pharmacy, Cairo University, Kasr El-Eini Street, Cairo, 11562, Egypt. nerminsadik@yahoo.com
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.
Insights
Pomegranate extract can help prevent colon cancer by regulating Wnt signalling pathways. This dietary agent normalizes key gene expressions, reduces tumour incidence, and improves survival rates in preclinical models.
Area of Science:
- Oncology
- Molecular Biology
- Dietary Interventions
Background:
- Wnt signalling pathway dysregulation is a key factor in colon cancer development.
- Identifying dietary agents to modulate Wnt signalling is crucial for cancer prevention strategies.
Purpose of the Study:
- To investigate the potential of pomegranate extract as a dietary agent to suppress colon cancer.
- To analyze the effect of pomegranate extract on Wnt signalling pathway key players in a rat model.
Main Methods:
- Utilized a 1,2-dimethylhydrazine dihydrochloride (DMH)-induced rat colon carcinogenesis model.
- Assessed Wnt signalling gene expression using reverse transcription polymerase chain reaction (RT-PCR).
- Evaluated tumour incidence, survival rates, and serum tumour markers (CEA).
Main Results:
- DMH-induced colon cancer showed aberrant Wnt gene expression (up-regulation of Wnt5a, β-catenin, c-myc, cyclin D1; down-regulation of APC, axin1).
- Pomegranate extract normalized these Wnt gene alterations in DMH-treated rats.
- Pomegranate extract significantly reduced tumour incidence, improved survival, and lowered CEA levels.
Conclusions:
- Standardized pomegranate extract demonstrates significant potential for colon cancer prevention.
- Pomegranate extract effectively modulates Wnt signalling pathways implicated in carcinogenesis.
- Dietary intervention with pomegranate extract offers a promising strategy for colon cancer suppression.
