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Green Tea Polyphenols Inhibit Colorectal Tumorigenesis in Azoxymethane-Treated F344 Rats
Xingpei Hao1,2, Hang Xiao1,3, Jihyeung Ju1,4
1a Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology , Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey , Piscataway , New Jersey , USA.
Abstract:
In studying the cancer-preventive activities of green tea polyphenols, we previously demonstrated that dietary administration of polyphenon E (PPE) inhibited the formation of aberrant crypt foci (ACF) in the colon of azoxymethane (AOM)-treated F344 rats. Herein, we reported cancer-preventive activity of PPE using colorectal cancer as an end point. F344 rats were given two weekly injections of AOM, and then maintained on a 20% high-fat diet with or without 0.24% PPE for 34 wk. In the control group, 83% of rats developed colorectal tumors. Dietary PPE treatment significantly increased the plasma and colonic levels of tea polyphenols, and decreased tumor multiplicity and tumor size. Histological analysis indicated that PPE significantly decreased the incidence of adenocarcinoma, and the multiplicity of adenocarcinoma as well as the multiplicity of adenoma. PPE treatment significantly decreased plasma levels of proinflammatory eicosanoids, prostaglandin E2, and leukotriene B4. It also decreased β-catenin nuclear expression, induced apoptosis, and increased expression levels of RXRα, β, and γ in adenocarcinomas. In conclusion, our results convincingly demonstrated the inhibitory effects of orally administered PPE on colon carcinogenesis in AOM-treated rats and suggested possible biomarkers for the biological effects of green tea polyphenols.
Insights
Green tea polyphenols (PPE) significantly inhibited colorectal cancer in rats by reducing tumor size and incidence. This study highlights PPE
Area of Science:
- Oncology
- Nutrition
- Green Tea Research
Background:
- Green tea polyphenols (PPE) have shown cancer-preventive properties.
- Previous studies indicated PPE inhibits aberrant crypt foci (ACF) formation in the colon.
Purpose of the Study:
- To evaluate the cancer-preventive activity of PPE in a rat model of colorectal cancer.
- To investigate the effects of PPE on tumor development and molecular markers.
Main Methods:
- Fischer 344 rats were administered azoxymethane (AOM) and a high-fat diet, with or without PPE.
- Tumor multiplicity, size, incidence, and histological analyses were performed.
- Plasma and colonic levels of tea polyphenols, eicosanoids, and specific protein expressions were measured.
Main Results:
- Dietary PPE significantly reduced colorectal tumor incidence (83% in control vs. lower in PPE group) and size.
- PPE decreased adenocarcinoma and adenoma multiplicity and incidence.
- PPE treatment lowered plasma prostaglandin E2 and leukotriene B4, reduced beta-catenin nuclear expression, induced apoptosis, and increased RXR expression.
Conclusions:
- Orally administered PPE demonstrates significant inhibitory effects on colon carcinogenesis in AOM-treated rats.
- PPE's effects involve modulation of inflammatory pathways, beta-catenin signaling, apoptosis, and retinoid X receptor expression.
- Findings suggest potential biomarkers for green tea polyphenol's biological effects in cancer prevention.
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