The effect of dietary polyphenols on the epigenetic regulation of gene expression in MCF7 breast cancer cells.
The CpG island methylator phenotype is characterized by DNA hypermethylation in the promoters of several suppressor genes associated with the inactivation of various pathways involved in tumorigenesis. DNA methylation is catalyzed by specific DNA methyltransferases (DNMTs). Dietary phytochemicals particularly catechol-containing polyphenols were shown to inhibit these enzymes and reactivate epigenetically silenced genes. The aim of this study was to evaluate the effect of a wide range of dietary phytochemicals on the activity and expression of DNMTs in human breast cancer MCF7 cell line and their effect on DNA and histone H3 methylation. All phytochemicals inhibited the DNA methyltransferase activity with betanin being the weakest while rosmarinic and ellagic acids were the most potent modulators (up to 88% inhibition). While decitabine led to a partial demethylation and reactivation of the genes, none of the tested phytochemicals affected the methylation pattern or the expression of RASSF1A, GSTP1 or HIN1 in MCF7 cells. The global methylation of histone H3 was not affected by any of the tested phytochemicals or decitabine. The results of our study may suggest that non-nucleoside agents are not likely to be effective epigenetic modulators, in our experimental model at least. However, a long-term exposure to these chemicals in diet might potentially lead to an effect, which can be sufficient for cancer chemoprevention.
Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, Poznan, Poland.
Jarosław
J
Paluszczak
Violetta
V
Krajka-Kuźniak
Wanda
W
Baer-Dubowska
D000970:Antineoplastic Agents / Q000494:pharmacology*; D050859:Betacyanins / Q000494:pharmacology; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D002396:Catechols / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002934:Cinnamates / Q000494:pharmacology; D019175:DNA Methylation / Q000187:drug effects; D015257:DNA-Cytosine Methylases / Q000187:drug effects / Q000378:metabolism; D053630:Depsides / Q000494:pharmacology; D004032:Diet; D044127:Epigenesis, Genetic / Q000187:drug effects*; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006657:Histones / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D010636:Phenols / Q000494:pharmacology*; D010945:Plants, Edible; D059808:Polyphenols; D000097123:Rosmarinic Acid
D000970:Antineoplastic Agents; D050859:Betacyanins; D002396:Catechols; D002934:Cinnamates; D015257:DNA-Cytosine Methylases; D053630:Depsides; D005419:Flavonoids; D006657:Histones; D010636:Phenols; D059808:Polyphenols; D000097123:Rosmarinic Acid; C020228:betanin