title: Dietary phytochemical PEITC restricts tumor development via modulation of epigenetic writers and erasers.
abstract: Dietary intake of bioactive phytochemicals including the cruciferous vegetable derivative phenethyl isothiocyanate (PEITC) can reduce risk of human cancers, but possible epigenetic mechanisms of these effects are yet unknown. We therefore sought to identify the molecular basis of PEITC-mediated epigenetic tumor restriction. Colon cancer cells treated with low-dose PEITC for >1 month exhibited stable alterations in expression profile of epigenetic writers/erasers and chromatin-binding of histone deacetylases (HDACs) and Polycomb-group (PcG) proteins. Sustained PEITC exposure not only blocked HDAC binding to euchromatin but was also associated with hypomethylation of PcG target genes that are typically hypermethylated in cancer. Furthermore, PEITC treatment induced expression of pro-apoptotic genes in tumor cells, which was partially reversed by overexpression of PcG member BMI-1, suggesting opposing roles for PEITC and PcG proteins in control of tumor progression. These data demonstrate that PEITC regulates chromatin binding of key epigenetic writers/erasers and PcG complexes to restrict tumor development.
authors.affiliation: School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, 637551 Singapore.
authors.forename: Jung Eun
authors.initials: JE
authors.lastname: Park
authors.affiliation: School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, 637551 Singapore.
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Institute of Medical Biology, A*STAR, 8A Biomedical Grove, #05-05 Immunos, 138648 Singapore.
authors.forename: Sai Kiang
authors.initials: SK
authors.lastname: Lim
authors.affiliation: School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, 637551 Singapore.
authors.forename: James P
authors.initials: JP
authors.lastname: Tam
authors.affiliation: Food Quality and Design Group, Department of Agrotechnology and Food Sciences, Wageningen University, PO Box 8129, 6700 EV Wageningen, Netherlands.
authors.forename: Matthijs
authors.initials: M
authors.lastname: Dekker
authors.affiliation: Department of Food Science and Human Nutrition, University of Illinois, 472 Bevier Hall, 905 S. Goodwin, Urbana IL 61801, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.affiliation: School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, 637551 Singapore.
authors.forename: Siu Kwan
authors.initials: SK
authors.lastname: Sze
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D000072224:Bcl-2-Like Protein 11 / Q000378:metabolism; D063646:Carcinogenesis / Q000187:drug effects / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology; D019175:DNA Methylation / Q000235:genetics; D004032:Diet; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D044127:Epigenesis, Genetic / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D063990:Gene Ontology; D006657:Histones / Q000378:metabolism; D017879:Isothiocyanates / Q000494:pharmacology*; D008819:Mice, Nude; D010641:Phenotype; D064209:Phytochemicals / Q000494:pharmacology*; D063146:Polycomb-Group Proteins / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D000072224:Bcl-2-Like Protein 11; D006657:Histones; D017879:Isothiocyanates; D064209:Phytochemicals; D063146:Polycomb-Group Proteins; C058305:phenethyl isothiocyanate