The effects of flavonoids, green tea polyphenols and coffee on DMBA induced LINE-1 DNA hypomethylation

PLoS One. 2021 Apr 20;16(4):e0250157. doi: 10.1371/journal.pone.0250157. eCollection 2021.

Abstract

The intake of carcinogenic and chemopreventive compounds are important nutritional factors related to the development of malignant tumorous diseases. Repetitive long interspersed element-1 (LINE-1) DNA methylation pattern plays a key role in both carcinogenesis and chemoprevention. In our present in vivo animal model, we examined LINE-1 DNA methylation pattern as potential biomarker in the liver, spleen and kidney of mice consuming green tea (Camellia sinensis) extract (catechins 80%), a chinese bayberry (Morella rubra) extract (myricetin 80%), a flavonoid extract (with added resveratrol) and coffee (Coffee arabica) extract. In the organs examined, carcinogen 7,12-dimethylbenz(a)anthracene (DMBA)-induced hypomethylation was prevented by all test materials except chinese bayberry extract in the kidneys. Moreover, the flavonoid extract caused significant hypermethylation in the liver compared to untreated controls and to other test materials. The tested chemopreventive substances have antioxidant, anti-inflammatory properties and regulate molecular biological signaling pathways. They increase glutathione levels, induce antioxidant enzymes, which decrease free radical damage caused by DMBA, and ultimately, they are able to increase the activity of DNA methyltransferase enzymes. Furthermore, flavonoids in the liver may inhibit the procarcinogen to carcinogen activation of DMBA through the inhibition of CYP1A1 enzyme. At the same time, paradoxically, myricetin can act as a prooxidant as a result of free radical damage, which can explain that it did not prevent hypomethylation in the kidneys. Our results demonstrated that LINE-1 DNA methylation pattern is a useful potential biomarker for detecting and monitoring carcinogenic and chemopreventive effects of dietary compounds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticarcinogenic Agents / pharmacology
  • Camellia sinensis / drug effects
  • Carcinogens / pharmacology
  • Catechin / pharmacology
  • Coffee / chemistry
  • DNA / metabolism
  • DNA Methylation / drug effects*
  • Female
  • Flavonoids / pharmacology
  • Glutathione / pharmacology
  • Kidney / drug effects
  • Liver / drug effects
  • Long Interspersed Nucleotide Elements / drug effects*
  • Long Interspersed Nucleotide Elements / genetics
  • Mice
  • Mice, Inbred CBA
  • Myrica / chemistry
  • Phenols / pharmacology
  • Plant Extracts / pharmacology*
  • Polyphenols / pharmacology
  • Spleen / drug effects
  • Tea / chemistry
  • gamma-Aminobutyric Acid / analogs & derivatives

Substances

  • Anticarcinogenic Agents
  • Carcinogens
  • Coffee
  • Flavonoids
  • Phenols
  • Plant Extracts
  • Polyphenols
  • Tea
  • gamma-Aminobutyric Acid
  • Catechin
  • DNA
  • 4-(dimethylamino)butyric acid
  • Glutathione

Grants and funding

This work was supported by the Higher Education Institutional Excellence Programme of the Ministry for Innovation and Technology in Hungary, within the framework of the “Innovation for the sustainable life and environment” thematic programme of the University of Pecs. The authors received no specific funding for this work.