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Mechanisms of cancer prevention by tea polyphenols based on inhibition of TNF-alpha expression
M Suganuma1, E Sueoka, N Sueoka
1Saitama Cancer Center Research Institute, Japan.
Abstract:
Among various biochemical and biological activities of tea polyphenols, we believe inhibition of the expression and release of tumor necrosis factor-alpha (TNF-alpha) is crucial, since our study with TNF-alpha-deficient mice has revealed that TNF-alpha is an essential factor in tumor promotion. We found that EGCG dose-dependently inhibited AP-1 and NF-kappaB activation in BALB/3T3 cells treated with okadaic acid, resulting in inhibition of TNF-alpha gene expression. Furthermore, treatment with 0.1% green tea extract in drinking water reduced TNF-alpha gene expression as well as TNF-alpha protein level in the lung of TNF-alpha transgenic mice; and IL-1beta and IL-10 gene expression in the lung was also inhibited by treatment with green tea extract, indicating that green tea inhibits both TNF-alpha and the cytokines induced by TNF-alpha in organs. We recently found synergistic effects of EGCG and cancer preventive agents such as tamoxifen and sulindac, on cancer preventive activity. Taken together, the results show that green tea is efficacious as a non-toxic cancer preventive for humans.
Insights
Green tea extract, particularly EGCG, inhibits tumor necrosis factor-alpha (TNF-alpha) production, a key factor in tumor promotion. This suggests green tea
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Tea polyphenols possess various biological activities.
- Tumor necrosis factor-alpha (TNF-alpha) plays a crucial role in tumor promotion.
- TNF-alpha-deficient mice studies highlight its essential role.
Purpose of the Study:
- To investigate the inhibitory effects of green tea polyphenols, specifically EGCG, on TNF-alpha expression and release.
- To determine the role of EGCG in modulating AP-1 and NF-kappaB activation.
- To evaluate the cancer-preventive efficacy of green tea extract in vivo.
Main Methods:
- Treatment of BALB/3T3 cells with okadaic acid and EGCG.
- Analysis of AP-1 and NF-kappaB activation.
- Administration of green tea extract to TNF-alpha transgenic mice.
- Measurement of TNF-alpha, IL-1beta, and IL-10 gene and protein expression in lung tissue.
- Assessment of synergistic effects with tamoxifen and sulindac.
Main Results:
- EGCG dose-dependently inhibited AP-1 and NF-kappaB activation, leading to reduced TNF-alpha gene expression.
- Green tea extract administration significantly reduced TNF-alpha gene and protein levels in the lungs of transgenic mice.
- Green tea extract also inhibited the expression of IL-1beta and IL-10, cytokines induced by TNF-alpha.
- Synergistic cancer-preventive effects were observed between EGCG and agents like tamoxifen and sulindac.
Conclusions:
- Green tea polyphenols, particularly EGCG, effectively inhibit TNF-alpha, a critical factor in tumor promotion.
- Green tea extract demonstrates efficacy in reducing TNF-alpha and associated cytokine expression in vivo.
- Green tea shows promise as a non-toxic, efficacious cancer preventive agent for humans.
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