Protective effects of coffee against oxidative stress induced by the tobacco carcinogen benzo[α]pyrene

Free Radic Biol Med. 2017 Jul;108:66-76. doi: 10.1016/j.freeradbiomed.2017.03.006. Epub 2017 Mar 12.

Abstract

Aims: Coffee consumption has been epidemiologically associated with a lower risk for liver cirrhosis and cancer. UDP-glucuronosyltransferases (UGT1A) catalyze the detoxification of reactive metabolites thereby acting as indirect antioxidants. Aim of the study was to examine UGT1A regulation in response to Benzo[α]pyrene (BaP) to elucidate the potentially protective effects of coffee on BaP-induced oxidative stress and toxicity.

Results: In cell culture (HepG2, KYSE70 cells) and in htgUGT1A-WT mice, UGT1A transcription was activated by BaP, while it was reduced or absent htgUGT1A-SNP (containing 10 commonly occurring UGT1A-SNPs) mice. siRNA-mediated knockdown identified aryl hydrocarbon receptor (AhR) and nuclear factor erythroid2-related factor-2 (Nrf2) as mediators of BaP-induced UGT1A upregulation. Exposure to coffee led to a reduction of BaP-induced production of reactive oxygen species in vitro and in htgUGT1A-WT and -SNP mice. After UGT1A silencing by UGT1A-specific siRNA in cell culture, the coffee-mediated reduction of ROS production was significantly impaired compared to UGT1A expressing cells.

Conclusion: A common UGT1A haplotype, prevalent in 9% (homozygous) of the White population, significantly impairs the expression of UGT1A enzymes in response to the putative tobacco carcinogen BaP and is likely to represent a significant risk factor for reduced detoxification and increased genotoxicity. Coffee was demonstrated to inhibit BaP-induced production of oxidative stress by UGT1A activation, and is therefore an attractive candidate for chemoprotection in risk groups for HCC or other tumors.

Keywords: BaP; Coffee; Glucuronidation; Oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Benzopyrenes / toxicity
  • Carcinoma, Hepatocellular / diet therapy
  • Carcinoma, Hepatocellular / epidemiology*
  • Carcinoma, Hepatocellular / genetics
  • Coffea*
  • Coffee / metabolism*
  • Eating
  • European Continental Ancestry Group
  • Gene Expression Regulation, Neoplastic
  • Genotype
  • Glucuronosyltransferase / genetics
  • Glucuronosyltransferase / metabolism*
  • Hep G2 Cells
  • Humans
  • Liver Cirrhosis / diet therapy
  • Liver Cirrhosis / epidemiology*
  • Liver Cirrhosis / genetics
  • Liver Neoplasms / diet therapy
  • Liver Neoplasms / epidemiology*
  • Liver Neoplasms / genetics
  • Male
  • Mice
  • Mice, Transgenic
  • Oxidative Stress
  • Polymorphism, Single Nucleotide
  • Prevalence
  • RNA, Small Interfering / genetics
  • Reactive Oxygen Species / metabolism
  • Receptors, Aryl Hydrocarbon / genetics
  • Receptors, Aryl Hydrocarbon / metabolism
  • Risk
  • Tobacco Smoking / adverse effects

Substances

  • AHR protein, human
  • Basic Helix-Loop-Helix Transcription Factors
  • Benzopyrenes
  • Coffee
  • RNA, Small Interfering
  • Reactive Oxygen Species
  • Receptors, Aryl Hydrocarbon
  • UGT1A1 enzyme
  • Glucuronosyltransferase