Lack of evidence for green tea polyphenols as DNA methylation inhibitors in murine prostate.
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.
Morey Kinney
Shannon R
SR
Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, New York, USA.
Zhang
Wa
W
Pascual
Marien
M
Greally
John M
JM
Gillard
Bryan M
BM
Karasik
Ellen
E
Foster
Barbara A
BA
Karpf
Adam R
AR
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000818:Animals; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000502:physiology; D019175:DNA Methylation; D005419:Flavonoids / Q000493:pharmacokinetics / Q000494:pharmacology*; D006160:Guanosine Triphosphate / Q000378:metabolism; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010636:Phenols / Q000493:pharmacokinetics / Q000494:pharmacology*; D059808:Polyphenols; D011467:Prostate / Q000378:metabolism / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013662:Tea; D014018:Tissue Distribution
D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D012333:RNA, Messenger; D013662:Tea; D006160:Guanosine Triphosphate; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases