title: Epigenetic impact of dietary isothiocyanates in cancer chemoprevention.
abstract: OBJECTIVE
  There is growing evidence that cancer chemopreventive agents including isothiocyanates (ITCs) from cruciferous vegetables target epigenetic mechanisms. The present report will summarize novel findings of ITCs on histone deacetylase activity, DNA methylation, and short noncoding microRNAs, focusing on sulforaphane (SFN) from broccoli and phenethylisothiocyanate from watercress.
  
  
  RESULTS
  In a human intervention study, broccoli sprouts led to more efficient histone deacetylase inhibition in blood cells than a broccoli sprout supplement, correlating with higher levels of urinary ITC metabolites. A proteomics study with ¹⁴C-labeled ITCs revealed among others a direct interaction with histones and chromatin-modulating proteins. The well investigated Kelch-like erythroid-cell-derived protein with CNC homology-associated protein 1/nuclear factor erythroid 2-related factor 2/antioxidant-response element pathway is both affected by and mechanistically involved in epigenetic activities of ITCs. Accordingly, reduction of oxidative stress is shown to prevent hypertension-associated global hypomethylation in rats. Combination of SFN with (-)-epigallocatechin gallate as a demethylating agent is identified as an effective approach for re-expression of estrogen receptor in hormone negative breast cancer. Induction of miR-200c by SFN prevents epithelial-mesenchymal-transition and could be relevant for prevention of metastases.
  
  
  CONCLUSIONS
  The last year has identified interesting areas of ITCs affecting epigenetic mechanisms that will have implications for translational cancer (prevention) research once validated in animal studies and human intervention studies.
authors: Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Heidelberg, Germany. c.gerhauser@dkfz.de
authors: Clarissa
authors: C
authors: Gerhauser
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D001937:Brassica / Q000737:chemistry; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology; D018890:Chemoprevention; D019175:DNA Methylation / Q000187:drug effects; D004032:Diet; D044127:Epigenesis, Genetic; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D017879:Isothiocyanates / Q000494:pharmacology*; D000072019:Kelch-Like ECH-Associated Protein 1; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics* / Q000517:prevention & control*; D015398:Signal Transduction; D013454:Sulfoxides
chemical_list: D016588:Anticarcinogenic Agents; D056572:Histone Deacetylase Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D017879:Isothiocyanates; C431364:KEAP1 protein, human; D000072019:Kelch-Like ECH-Associated Protein 1; D035683:MicroRNAs; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D013454:Sulfoxides; C058305:phenethyl isothiocyanate; D002392:Catechin; C045651:epigallocatechin gallate; D006655:Histone Deacetylases; C016766:sulforaphane