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Updated: Jun 18, 2026
An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
Lack of evidence for green tea polyphenols as DNA methylation inhibitors in murine prostate
Shannon R Morey Kinney1, Wa Zhang, Marien Pascual
1Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, New York, USA.
Abstract:
Green tea polyphenols (GTP) have been reported to inhibit DNA methylation in cultured cells. Here, we tested whether oral consumption of GTPs affects normal or cancer-specific DNA methylation in vivo, using mice. Wild-type (WT) and transgenic adenocarcinoma of mouse prostate (TRAMP) mice were given 0.3% GTPs in drinking water beginning at 4 weeks of age. To monitor DNA methylation, we measured 5-methyl-deoxycytidine (5mdC) levels, methylation of the B1 repetitive element, and methylation of the Mage-a8 gene. Each of these parameters were unchanged in prostate, gut, and liver from WT mice at both 12 and 24 weeks of age, with the single exception of a decrease of 5mdC in the liver at 12 weeks. In GTP-treated TRAMP mice, 5mdC levels and the methylation status of four loci hypermethylated during tumor progression were unaltered in TRAMP prostates at 12 or 24 weeks. Quite surprisingly, GTP treatment did not inhibit tumor progression in TRAMP mice, although known pharmacodynamic markers of GTPs were altered in both WT and TRAMP prostates. We also administered 0.1%, 0.3%, or 0.6% GTPs to TRAMP mice for 12 weeks and measured 5mdC levels and methylation of B1 and Mage-a8 in prostate, gut, and liver tissues. No dose-dependent alterations in DNA methylation status were observed. Genome-wide DNA methylation profiling using the HpaII tiny fragment enrichment by ligation-mediated PCR assay also revealed no significant hypomethylating effect of GTP. These data indicate that oral administration of GTPs does not affect normal or cancer-specific DNA methylation in the murine prostate.
Insights
Oral consumption of green tea polyphenols (GTP) did not alter DNA methylation in mice, even in prostate cancer models. This study investigated the in vivo effects of GTP on DNA methylation, finding no significant changes in normal or cancerous tissues.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Green tea polyphenols (GTP) are known to inhibit DNA methylation in cell cultures.
- The in vivo effects of oral GTP consumption on DNA methylation remain largely uncharacterized.
Purpose of the Study:
- To investigate whether oral GTP administration affects normal or cancer-specific DNA methylation in vivo.
- To assess the impact of GTP on DNA methylation in prostate, gut, and liver tissues of wild-type and TRAMP mice.
Main Methods:
- Wild-type (WT) and TRAMP mice were administered 0.3% GTP in drinking water.
- DNA methylation was monitored by measuring 5-methyl-deoxycytidine (5mdC) levels, B1 repetitive element methylation, and Mage-a8 gene methylation.
- Genome-wide DNA methylation profiling was performed using the HpaII tiny fragment enrichment by ligation-mediated PCR assay.
Main Results:
- Oral GTP administration did not alter 5mdC levels or methylation status of key genes in WT or TRAMP mouse prostates, gut, or liver.
- A minor decrease in liver 5mdC was observed in WT mice at 12 weeks, but this was not dose-dependent or consistently observed.
- GTP treatment did not inhibit tumor progression in TRAMP mice, despite altering pharmacodynamic markers.
Conclusions:
- Oral administration of green tea polyphenols does not significantly affect normal or cancer-specific DNA methylation in the murine prostate.
- The in vitro hypomethylating effects of GTP may not translate to in vivo efficacy in the prostate.
