Lack of evidence for green tea polyphenols as DNA methylation inhibitors in murine prostate

Shannon R. Morey Kinney, Wa Zhang, Marien Pascual, John M. Greally, Bryan M. Gillard, Ellen Karasik, Barbara A. Foster, Adam R. Karpf

Research output: Contribution to journalArticle

35 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1065-1075
Number of pages11
JournalCancer Prevention Research
Volume2
Issue number12
DOIs
StatePublished - Dec 1 2009

Fingerprint

Polyphenols
Tea
DNA Methylation
Prostate
Transgenic Mice
Guanosine Triphosphate
Deoxycytidine
Adenocarcinoma
Methylation
Liver
Neoplasms
DNA Fingerprinting
Drinking Water
Ligation
Oral Administration
Cultured Cells
Genome
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Lack of evidence for green tea polyphenols as DNA methylation inhibitors in murine prostate. / Morey Kinney, Shannon R.; Zhang, Wa; Pascual, Marien; Greally, John M.; Gillard, Bryan M.; Karasik, Ellen; Foster, Barbara A.; Karpf, Adam R.

In: Cancer Prevention Research, Vol. 2, No. 12, 01.12.2009, p. 1065-1075.

Research output: Contribution to journalArticle

Morey Kinney, SR, Zhang, W, Pascual, M, Greally, JM, Gillard, BM, Karasik, E, Foster, BA & Karpf, AR 2009, 'Lack of evidence for green tea polyphenols as DNA methylation inhibitors in murine prostate', Cancer Prevention Research, vol. 2, no. 12, pp. 1065-1075. https://doi.org/10.1158/1940-6207.CAPR-09-0010
Morey Kinney SR, Zhang W, Pascual M, Greally JM, Gillard BM, Karasik E et al. Lack of evidence for green tea polyphenols as DNA methylation inhibitors in murine prostate. Cancer Prevention Research. 2009 Dec 1;2(12):1065-1075. https://doi.org/10.1158/1940-6207.CAPR-09-0010
Morey Kinney, Shannon R. ; Zhang, Wa ; Pascual, Marien ; Greally, John M. ; Gillard, Bryan M. ; Karasik, Ellen ; Foster, Barbara A. ; Karpf, Adam R. / Lack of evidence for green tea polyphenols as DNA methylation inhibitors in murine prostate. In: Cancer Prevention Research. 2009 ; Vol. 2, No. 12. pp. 1065-1075.
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