Dietary phytochemicals as epigenetic modifiers in cancer: Promise and challenges

Henikoff, 1997, Exploring and explaining epigenetic effects, Trends Genet., 13, 293, 10.1016/S0168-9525(97)01219-5 Hughes, 2014, Epigenetics: the sins of the father, Nature, 507, 22, 10.1038/507022a Payer, 2008, X chromosome dosage compensation: how mammals keep the balance, Annu. Rev. Genet., 42, 733, 10.1146/annurev.genet.42.110807.091711 Illingworth, 2008, A novel CpG island set identifies tissue-specific methylation at developmental gene loci, PLoS Biol., 6, e22, 10.1371/journal.pbio.0060022 Li, 1993, Role for DNA methylation in genomic imprinting, Nature, 366, 362, 10.1038/366362a0 Jones, 2001, The role of DNA methylation in mammalian epigenetics, Science, 293, 1068, 10.1126/science.1063852 Jarome, 2013, Histone lysine methylation: critical regulator of memory and behavior, Rev. Neurosci., 24, 375, 10.1515/revneuro-2013-0008 Peixoto, 2013, The role of histone acetylation in memory formation and cognitive impairments, Neuropsychopharmacology, 38, 62, 10.1038/npp.2012.86 Lubin, 2011, Epigenetic mechanisms: critical contributors to long-term memory formation, Neuroscientist, 17, 616, 10.1177/1073858410386967 Gos, 2013, Epigenetic mechanisms of gene expression regulation in neurological diseases, Acta Neurobiol. Exp. (Wars), 73, 19 Jones, 2002, The fundamental role of epigenetic events in cancer, Nat. Rev. Genet., 3, 415, 10.1038/nrg816 Stilling, 2011, The role of histone acetylation in age-associated memory impairment and Alzheimer’s disease, Neurobiol. Learn Mem., 96, 19, 10.1016/j.nlm.2011.04.002 Bruce, 2011, Epigenetic priming of the metabolic syndrome, Toxicol Mech Methods, 21, 353, 10.3109/15376516.2011.559370 Suter, 2009, Environmental influences on epigenetic profiles, Semin. Reprod. Med., 27, 380, 10.1055/s-0029-1237426 Jaenisch, 2003, Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals, Nat. Genet., 33, 245, 10.1038/ng1089 Choudhuri, 2011, From Waddington’s epigenetic landscape to small noncoding RNA: some important milestones in the history of epigenetics research, Toxicol. Mech. Methods, 21, 252, 10.3109/15376516.2011.559695 Issa, 2009, Targeting DNA methylation, Clin. Cancer Res., 15, 3938, 10.1158/1078-0432.CCR-08-2783 Dehan, 2009, DNA methylation and cancer diagnosis: new methods and applications, Exp. Rev. Mol. Diagn., 9, 651, 10.1586/erm.09.53 Link, 2010, Cancer chemoprevention by dietary polyphenols: promising role for epigenetics, Biochem. Pharmacol., 80, 1771, 10.1016/j.bcp.2010.06.036 Gerhauser, 2013, Cancer chemoprevention and nutriepigenetics: state of the art and future challenges, Top Curr. Chem., 329, 73, 10.1007/128_2012_360 Bestor, 2000, The DNA methyltransferases of mammals, Hum. Mol. Genet., 9, 2395, 10.1093/hmg/9.16.2395 Santi, 1983, On the mechanism of inhibition of DNA-cytosine methyltransferases by cytosine analogs, Cell, 33, 9, 10.1016/0092-8674(83)90327-6 Bird, 2002, DNA methylation patterns and epigenetic memory, Genes Dev., 16, 6, 10.1101/gad.947102 Yoder, 1997, DNA (cytosine-5)-methyltransferases in mouse cells and tissues: studies with a mechanism-based probe, J. Mol. Biol., 270, 385, 10.1006/jmbi.1997.1125 Okano, 1999, DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development, Cell, 99, 247, 10.1016/S0092-8674(00)81656-6 Bourc'his, 2001, Dnmt3L and the establishment of maternal genomic imprints, Science, 294, 2536, 10.1126/science.1065848 Hata, 2002, Dnmt3L cooperates with the Dnmt3 family of de novo DNA methyltransferases to establish maternal imprints in mice, Development, 129, 1983, 10.1242/dev.129.8.1983 Denis, 2011, Regulation of mammalian DNA methyltransferases: a route to new mechanisms, EMBO Rep., 12, 647, 10.1038/embor.2011.110 Watt, 1988, Cytosine methylation prevents binding to DNA of a HeLa cell transcription factor required for optimal expression of the adenovirus major late promoter, Genes Dev., 2, 1136, 10.1101/gad.2.9.1136 Hark, 2000, CTCF mediates methylation-sensitive enhancer-blocking activity at the H19/Igf2 locus, Nature, 405, 486, 10.1038/35013106 Tate, 1993, Effects of DNA methylation on DNA-binding proteins and gene expression, Curr. Opin. Genet Dev., 3, 226, 10.1016/0959-437X(93)90027-M Jones, 1998, Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription, Nat. Genet., 19, 187, 10.1038/561 Nan, 1998, Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex, Nature, 393, 386, 10.1038/30764 Feng, 2001, The MeCP1 complex represses transcription through preferential binding, remodeling, and deacetylating methylated nucleosomes, Genes Dev., 15, 827 Hendrich, 1998, Identification and characterization of a family of mammalian methyl-CpG binding proteins, Mol. Cell. Biol., 18, 6538, 10.1128/MCB.18.11.6538 Nan, 1993, Dissection of the methyl-CpG binding domain from the chromosomal protein MeCP2, Nucliic Acids Res., 21, 4886, 10.1093/nar/21.21.4886 Roos, 2016, Integrative DNA methylome analysis of pan-cancer biomarkers in cancer discordant monozygotic twin-pairs, Clin. Epigenetics., 8, 7, 10.1186/s13148-016-0172-y Bhat, 2016, Biological implications and therapeutic significance of DNA methylation regulated genes in cervical cancer, Biochimie, 121, 298, 10.1016/j.biochi.2015.12.018 Yen, 2016, DNA methylation, histone acetylation and methylation of epigenetic modifications as a therapeutic approach for cancers, Cancer Lett., 373, 185, 10.1016/j.canlet.2016.01.036 Luger, 1998, The histone tails of the nucleosome, Curr. Opin Genet Dev., 8, 140, 10.1016/S0959-437X(98)80134-2 Kornberg, 1999, Twenty-five years of the nucleosome, fundamental particle of the eukaryote chromosome, Cell, 98, 285, 10.1016/S0092-8674(00)81958-3 Strahl, 2000, The language of covalent histone modifications, Nature, 403, 41, 10.1038/47412 Struhl, 1998, Histone acetylation and transcriptional regulatory mechanisms, Genes Dev., 12, 599, 10.1101/gad.12.5.599 Bannister, 2011, Regulation of chromatin by histone modifications, Cell Res., 21, 381, 10.1038/cr.2011.22 Kuo, 1998, Roles of histone acetyltransferases and deacetylases in gene regulation, Bioessays, 20, 615, 10.1002/(SICI)1521-1878(199808)20:8<615::AID-BIES4>3.0.CO;2-H Sauve, 2006, The biochemistry of sirtuins, Annu. Rev. Biochem., 75, 435, 10.1146/annurev.biochem.74.082803.133500 Mottet, 2008, Histone deacetylases: target enzymes for cancer therapy, Clin. Exp. Metastasis, 25, 183, 10.1007/s10585-007-9131-5 Shi, 2007, Histone lysine demethylases: emerging roles in development, physiology and disease, Nat. Rev. Genet., 8, 829, 10.1038/nrg2218 Rice, 2001, Histone methylation versus histone acetylation: new insights into epigenetic regulation, Curr. Opin. Cell Biol., 13, 263, 10.1016/S0955-0674(00)00208-8 Upadhyay, 2011, Dynamics of histone lysine methylation: structures of methyl writers and erasers, Prog. Drug Res., 67, 107 Mir, 2016, Circulating autoantibodies in cancer patients have high specificity for glycoxidation modified histone H2A, Clin. Chim. Acta., 453, 48, 10.1016/j.cca.2015.12.004 Ma, 2016, Histone modifying enzymes: novel disease biomarkers and assay development, Expert Rev. Mol. Diagn., 11, 1 Deb, 2014, EZH2: not EZHY (Easy) to deal, Mol. Cancer Res., 12, 639, 10.1158/1541-7786.MCR-13-0546 Kouzarides, 2007, Chromatin modifications and their function, Cell, 128, 693, 10.1016/j.cell.2007.02.005 Suzuki, 2006, Epigenetic control using natural products and synthetic molecules, Curr. Med. Chem., 13, 935, 10.2174/092986706776361067 Costa, 2008, Non-coding RNAs, epigenetics and complexity, Gene, 410, 9, 10.1016/j.gene.2007.12.008 Peschansky, 2014, Non-coding RNAs as direct and indirect modulators of epigenetic regulation, Epigenetics, 9, 3, 10.4161/epi.27473 Zhou, 2010, Non-coding RNAs and their epigenetic regulatory mechanisms, Biol. Cell., 102, 645, 10.1042/BC20100029 Mattick, 2001, Non-coding RNAs: the architects of eukaryotic complexity, EMBO Rep., 2, 986, 10.1093/embo-reports/kve230 Szymanski, 2005, A new frontier for molecular medicine: noncoding RNAs, Biochim. Biophys. Acta, 1756, 65 Deb, 2013, Multifaceted role of EZH2 in breast and prostate tumorigenesis: epigenetics and beyond, Epigenetics, 8, 464, 10.4161/epi.24532 Sander, 2008, MYC stimulates EZH2 expression by repression of its negative regulator miR-26a, Blood, 112, 4202, 10.1182/blood-2008-03-147645 Varambally, 2008, Genomic loss of microRNA-101 leads to overexpression of histone methyltransferase EZH2 in cancer, Science, 322, 1695, 10.1126/science.1165395 Juan, 2009, Mir-214-dependent regulation of the polycomb protein Ezh2 in skeletal muscle and embryonic stem cells, Mol. Cell., 36, 61, 10.1016/j.molcel.2009.08.008 Liu, 2012, miR-200c inhibits melanoma progression and drug resistance through down-regulation of BMI-1, Am. J. Pathol., 181, 1823, 10.1016/j.ajpath.2012.07.009 Godlewski, 2008, Targeting of the Bmi-1 oncogene/stem cell renewal factor by microRNA-128 inhibits glioma proliferation and self-renewal, Cancer Res., 68, 9125, 10.1158/0008-5472.CAN-08-2629 Liz, 2016, lncRNAs and microRNAs with a role in cancer development, Biochim. Biophys. Acta, 1859, 169, 10.1016/j.bbagrm.2015.06.015 Fabris, 2016, The potential of MicroRNAs as prostate cancer biomarkers, Eur. Urol., 10.1016/j.eururo.2015.12.054 Wellner, 2009, The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs, Nat. Cell Biol., 11, 1487, 10.1038/ncb1998 Fabbri, 2007, MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B, Proc. Natl. Acad. Sci. U. S. A., 104, 15805, 10.1073/pnas.0707628104 Garzon, 2009, MicroRNA-29b induces global DNA hypomethylation and tumor suppressor gene reexpression in acute myeloid leukemia by targeting directly DNMT3A and 3B and indirectly DNMT1, Blood, 113, 6411, 10.1182/blood-2008-07-170589 Huang, 2011, Cancer chemoprevention by targeting the epigenome, Curr. Drug Targets., 12, 1925, 10.2174/138945011798184155 Russo, 2015, Dietary polyphenols and chromatin remodelling, Crit. Rev. Food Sci. Nutr., 10 Thakur, 2014, Plant phytochemicals as epigenetic modulators: role in cancer chemoprevention, AAPS J., 16, 151, 10.1208/s12248-013-9548-5 Hauser, 2008, Targeting epigenetic mechanisms: potential of natural products in cancer chemoprevention, Planta Med., 74, 1593, 10.1055/s-2008-1081347 Davis, 2008, Evidence for dietary regulation of microRNA expression in cancer cells, Nutr. Rev., 66, 477, 10.1111/j.1753-4887.2008.00080.x Li, 2010, Regulation of microRNAs by natural agents: an emerging field in chemoprevention and chemotherapy research, Pharm. Res., 27, 1027, 10.1007/s11095-010-0105-y Patel, 2007, Apigenin and cancer chemoprevention: progress, potential and promise (review), Int. J. Oncol., 30, 233 Birt, 2001, Dietary agents in cancer prevention: flavonoids and isoflavonoids, Pharmacol. Ther., 90, 157, 10.1016/S0163-7258(01)00137-1 Surh, 2003, Cancer chemoprevention with dietary phytochemicals, Nat. Rev. Cancer, 3, 768, 10.1038/nrc1189 Manach, 2004, Polyphenols: food sources and bioavailability, Am. J. Clin. Nutr., 79, 727, 10.1093/ajcn/79.5.727 Birt, 1986, Anti-mutagenesis and anti-promotion by apigenin, robinetin and indole-3-carbinol, Carcinogenesis, 7, 959, 10.1093/carcin/7.6.959 Wei, 1990, Inhibitory effect of apigenin, a plant flavonoid, on epidermal ornithine decarboxylase and skin tumor promotion in mice, Cancer Res., 50, 499 Choi, 2014, Effects of C-glycosylation on anti-diabetic, anti-Alzheimer's disease and anti-inflammatory potential of apigenin, Food Chem. Toxicol., 64, 27, 10.1016/j.fct.2013.11.020 Fang, 2007, Dietary polyphenols may affect DNA methylation, J. Nutr., 137, 223s, 10.1093/jn/137.1.223S Pandey, 2012, Plant flavone apigenin inhibits HDAC and remodels chromatin to induce growth arrest and apoptosis in human prostate cancer cells: in vitro and in vivo study, Mol. Carcinog., 51, 952, 10.1002/mc.20866 Paredes-Gonzalez, 2014, Apigenin reactivates Nrf2 anti-oxidative stress signaling in mouse skin epidermal JB6 P+ cells through epigenetics modifications, AAPS J., 16, 727, 10.1208/s12248-014-9613-8 Prasad, 2014, Curcumin a component of golden spice: from bedside to bench and back, Biotechnol. Adv., 32, 1053, 10.1016/j.biotechadv.2014.04.004 Bar-Sela, 2010, Curcumin as an anti-cancer agent: review of the gap between basic and clinical applications, Curr. Med. Chem., 17, 190, 10.2174/092986710790149738 Sharma, 2005, Curcumin: the story so far, Eur. J. Cancer., 41, 1955, 10.1016/j.ejca.2005.05.009 Teiten, 2010, Curcumin-the paradigm of a multi-target natural compound with applications in cancer prevention and treatment, Toxins (Basel), 2, 128, 10.3390/toxins2010128 Fu, 2010, Development of curcumin as an epigenetic agent, Cancer, 116, 4670, 10.1002/cncr.25414 Medina-Franco, 2011, Natural products as DNA methyltransferase inhibitors: a computer-aided discovery approach, Mol. Divers, 15, 293, 10.1007/s11030-010-9262-5 Liu, 2009, Curcumin is a potent DNA hypomethylation agent, Bioorg Med. Chem. Lett., 19, 706, 10.1016/j.bmcl.2008.12.041 Bora-Tatar, 2009, Molecular modifications on carboxylic acid derivatives as potent histone deacetylase inhibitors: activity and docking studies, Bioorg Med. Chem., 17, 5219, 10.1016/j.bmc.2009.05.042 Liu, 2005, Curcumin a potent anti-tumor reagent, is a novel histone deacetylase inhibitor regulating B-NHL cell line Raji proliferation, Acta Pharmacol. Sin., 26, 603, 10.1111/j.1745-7254.2005.00081.x Chen, 2007, Curcumin, both histone deacetylase and p300/CBP-specific inhibitor, represses the activity of nuclear factor kappa B and Notch 1 in Raji cells, Basic Clin. Pharmacol. Toxicol., 101, 427, 10.1111/j.1742-7843.2007.00142.x Dekker, 2009, Histone acetyl transferases as emerging drug targets, Drug Discov. Today, 14, 942, 10.1016/j.drudis.2009.06.008 Marcu, 2006, Curcumin is an inhibitor of p300 histone acetylatransferase, Med. Chem., 2, 169, 10.2174/157340606776056133 Balasubramanyam, 2004, Curcumin, a novel p300/CREB-binding protein-specific inhibitor of acetyltransferase, represses the acetylation of histone/nonhistone proteins and histone acetyltransferase-dependent chromatin transcription, J. Biol. Chem., 279, 51163, 10.1074/jbc.M409024200 Guo, 2015, Curcumin inhibits anchorage-independent growth of HT29 human colon cancer cells by targeting epigenetic restoration of the tumor suppressor gene DLEC1, Biochem. Pharmacol., 9, 69, 10.1016/j.bcp.2015.01.009 Sharma, 2015, Curcumin-Mediated reversal of p15 gene promoter methylation: implication in anti-Neoplastic action against acute lymphoid leukaemia cell line, Folia Biol. (Praha), 61, 81 Sun, 2008, Curcumin (diferuloylmethane) alters the expression profiles of microRNAs in human pancreatic cancer cells, Mol. Cancer Ther., 7, 464, 10.1158/1535-7163.MCT-07-2272 Ali, 2010, Gemcitabine sensitivity can be induced in pancreatic cancer cells through modulation of miR-200 and miR-21 expression by curcumin or its analogue CDF, Cancer Res., 70, 3606, 10.1158/0008-5472.CAN-09-4598 Jiang, 2015, Curcumin reactivates silenced tumor suppressor gene RARβ by reducing DNA methylation, Phytother. Res., 29, 1237, 10.1002/ptr.5373 Zamani, 2015, Dendrosomal curcumin increases expression of the long non coding RNA gene MEG3 via up-regulation of epi-miRs in hepatocellular cancer, Phytomedicine, 22, 961, 10.1016/j.phymed.2015.05.071 Butt, 2009, Green tea: nature’s defense against malignancies, Crit. Rev. Food Sci. Nutr., 49, 463, 10.1080/10408390802145310 Shankar, 2007, Green tea polyphenols: biology and therapeutic implications in cancer, Front. Biosci., 12, 4881, 10.2741/2435 Fang, 2003, Tea polyphenol (−)-epigallocatechin-3-gallate inhibits DNA methyltransferase and reactivates methylation-silenced genes in cancer cell lines, Cancer Res., 63, 7563 Pandey, 2010, Promoter demethylation and chromatin remodeling by green tea polyphenols leads to re-expression of GSTP1 in human prostate cancer cells, Int. J. Cancer., 126, 2520 Thakur, 2012, Green tea polyphenols causes cell cycle arrest and apoptosis in prostate cancer cells by suppressing class I histone deacetylases, Carcinogenesis, 33, 377, 10.1093/carcin/bgr277 Li, 2010, Synergistic epigenetic reactivation of estrogen receptor-alpha (ERalpha) by combined green tea polyphenol and histone deacetylase inhibitor in ERalpha-negative breast cancer cells, Mol. Cancer, 9, 274, 10.1186/1476-4598-9-274 Nandakumar, 2011, (−)-Epigallocatechin-3-gallate reactivates silenced tumor suppressor genes, Cip1/p21 and p16INK4a, by reducing DNA methylation and increasing histones acetylation in human skin cancer cells, Carcinogenesis, 32, 537, 10.1093/carcin/bgq285 Balasubramanian, 2010, The Bmi-1 polycomb protein antagonizes the (−)-epigallocatechin-3-gallate-dependent suppression of skin cancer cell survival, Carcinogenesis, 31, 496, 10.1093/carcin/bgp314 Choudhury, 2011, (−)-Epigallocatechin-3-gallate and DZNep reduce polycomb protein level via a proteasome-dependent mechanism in skin cancer cells, Carcinogenesis, 32, 1525, 10.1093/carcin/bgr171 Deb, 2014, Epigenetic induction of tissue inhibitor of matrix metalloproteinase-3 by green tea polyphenols in breast cancer cells, Mol. Carcinog., 54, 485, 10.1002/mc.22121 Khan, 2015, (−)-Epigallocatechin-3 gallate reverses the expression of various tumor suppressor genes by inhibiting DNA methyltransferases and histone deacetylases in human cervical cancer cells, Oncol. Rep., 33, 1976, 10.3892/or.2015.3802 Zhou, 2015, Epigallocatechin-3-gallate inhibits the invasion of salivary adenoid cystic carcinoma cells by reversing the hypermethylation status of the RECK gene, Mol. Med. Rep., 12, 6031, 10.3892/mmr.2015.4213 Jha, 2015, Natural compounds DNA methyltransferase inhibitors in oral squamous cell carcinoma, Appl. Biochem. Biotechnol., 177, 577, 10.1007/s12010-015-1768-y Chen, 2015, A genome-wide study of DNA methylation modified by epigallocatechin-3-gallate in the CAL-27 cell line, Mol. Med. Rep., 12, 5886, 10.3892/mmr.2015.4118 Coward, 1993, Genistein, daidzein, and their β-glycoside conjugates: antitumor isoflavones in soybean foods from American and Asian diets, J. Agric. Food Chem., 41, 1961, 10.1021/jf00035a027 Kaufman, 1997, A comparative survey of leguminous plants as sources of the isoflavones, genistein and daidzein: implications for human nutrition and health, J. Altern. Complement Med., 3, 7, 10.1089/acm.1997.3.7 Banerjee, 2008, Multi-targeted therapy of cancer by genistein, Cancer Lett., 269, 226, 10.1016/j.canlet.2008.03.052 Fang, 2005, Reversal of hypermethylation and reactivation of p16INK4a, RARbeta, and MGMT genes by genistein and other isoflavones from soy, Clin. Cancer Res., 11, 7033, 10.1158/1078-0432.CCR-05-0406 Li, 2009, Genistein depletes telomerase activity through cross-talk between genetic and epigenetic mechanisms, Int. J. Cancer, 125, 286, 10.1002/ijc.24398 King-Batoon, 2008, Modulation of gene methylation by genistein or lycopene in breast cancer cells, Environ. Mol. Mutagen, 49, 36, 10.1002/em.20363 Majid, 2009, BTG3 tumor suppressor gene promoter demethylation, histone modification and cell cycle arrest by genistein in renal cancer, Carcinogenesis, 30, 662, 10.1093/carcin/bgp042 Majid, 2010, Genistein reverses hypermethylation and induces active histone modifications in tumor suppressor gene B-Cell translocation gene 3 in prostate cancer, Cancer, 116, 66 Day, 2002, Genistein alters methylation patterns in mice, J. Nutr., 132, 2419, 10.1093/jn/132.8.2419S Hong, 2004, Isoflavones stimulate estrogen receptor-mediated core histone acetylation, Biochem. Biophys. Res. Commun., 317, 259, 10.1016/j.bbrc.2004.03.041 Majid, 2008, Genistein induces the p21WAF1/CIP1 and p16INK4a tumor suppressor genes in prostate cancer cells by epigenetic mechanisms involving active chromatin modification, Cancer Res., 68, 2736, 10.1158/0008-5472.CAN-07-2290 Basak, 2008, Genistein down-regulates androgen receptor by modulating HDAC6-Hsp90 chaperone function, Mol. Cancer Ther., 7, 3195, 10.1158/1535-7163.MCT-08-0617 Karsli-Ceppioglu, 2015, Genome-wide DNA methylation modified by soy phytoestrogens: role for epigenetic therapeutics in prostate cancer?, OMICS, 19, 209, 10.1089/omi.2014.0142 Mahmoud, 2015, Genistein increases estrogen receptor beta expression in prostate cancer via reducing its promoter methylation, J. Steroid Biochem. Mol. Biol., 152, 62, 10.1016/j.jsbmb.2015.04.018 Qin, 2009, Soy isoflavones have an antiestrogenic effect and alter mammary promoter hypermethylation in healthy premenopausal women, Nutr. Cancer, 61, 238, 10.1080/01635580802404196 Parker, 2009, Modulation of microRNA associated with ovarian cancer cells by genistein, Eur. J. Gynaecol. Oncol., 30, 616 Li, 2009, Up-regulation of miR-200 and let-7 by natural agents leads to the reversal of epithelial-to-mesenchymal transition in gemcitabine-resistant pancreatic cancer cells, Cancer Res., 69, 6704, 10.1158/0008-5472.CAN-09-1298 Sun, 2009, Genistein inhibits growth of human uveal melanoma cells and affects microRNA-27a and target gene expression, Oncol. Rep., 22, 563 Qin, 2015, Genistein inhibits human colorectal cancer growth and suppresses miR-95, Akt and SGK1, Cell Physiol. Biochem., 35, 2069, 10.1159/000374013 Avci, 2015, Genistein-induced mir-23b expression inhibits the growth of breast cancer cells, Contemp Oncol (Pozn), 19, 32 Rogan, 2006, The natural chemopreventive compound indole-3-carbinol: state of the science, In Vivo, 20, 221 Minich, 2007, A review of the clinical efficacy and safety of cruciferous vegetable phytochemicals, Nutr. Rev., 65, 259, 10.1111/j.1753-4887.2007.tb00303.x Acharya, 2010, Chemopreventive properties of indole-3-carbinol, diindolylmethane and other constituents of cardamom against carcinogenesis, Recent Pat. Food Nutr. Agric., 2, 166, 10.2174/1876142911002020166 Aggarwal, 2005, Molecular targets and anticancer potential of indole-3-carbinol and its derivatives, Cell Cycle, 4, 1201, 10.4161/cc.4.9.1993 Banerjee, 2011, Attenuation of multi-targeted proliferation-linked signaling by 3,3′-diindolylmethane (DIM): from bench to clinic, Mutat. Res., 728, 47, 10.1016/j.mrrev.2011.06.001 Li, 2010, Chemopreventive agent 3,3′-diindolylmethane selectively induces proteasomal degradation of class I histone deacetylases, Cancer Res., 70, 646, 10.1158/0008-5472.CAN-09-1924 Beaver, 2012, 3,3′-Diindolylmethane, but not indole-3-carbinol, inhibits histone deacetylase activity in prostate cancer cells, Toxicol. Appl. Pharmacol., 263, 345, 10.1016/j.taap.2012.07.007 Busbee, 2014, Natural indoles, indole-3-carbinol and 3,3'diindolymethane, inhibit T cell activation by staphylococcal enterotoxin B through epigenetic regulation involving HDAC expression, Toxicol. Appl. Pharmacol., 274, 7, 10.1016/j.taap.2013.10.022 Li, 2010, miR-146a suppresses invasion of pancreatic cancer cells, Cancer Res., 70, 1486, 10.1158/0008-5472.CAN-09-2792 Jin, 2010, 3,3′-Diindolylmethane negatively regulates Cdc25A and induces a G2/M arrest by modulation of microRNA 21 in human breast cancer cells, Anticancer Drugs, 21, 814, 10.1097/CAD.0b013e32833e53ea Wang, 2015, DATS suppresses growth of esophageal squamous cell carcinoma by regulation of ERK1/2, Clin. Lab., 61, 315 Chalabi, 2007, Expression profiling by whole-genome microarray hybridization reveals differential gene expression in breast cancer cell lines after lycopene exposure, Biochim. Biophys. Acta, 1769, 124, 10.1016/j.bbaexp.2007.01.007 Chalabi, 2006, Gene signature of breast cancer cell lines treated with lycopene, Pharmacogenomics, 7, 663, 10.2217/14622416.7.5.663 Fu, 2014, The effects of lycopene on the methylation of the GSTP1 promoter and global methylation in prostatic cancer cell lines PC3 and LNCaP, Int. J. Endocrinol., 2014, 620165, 10.1155/2014/620165 Iciek, 2009, Biological properties of garlic and garlic-derived organosulfur compounds, Environ. Mol. Mutagen., 50, 247, 10.1002/em.20474 Nian, 2009, Modulation of histone deacetylase activity by dietary isothiocyanates and allyl sulfides: studies with sulforaphane and garlic organosulfur compounds, Environ. Mol. Mutagen., 50, 213, 10.1002/em.20454 Lea, 1999, Increased acetylation of histones induced by diallyl disulfide and structurally related molecules, Int. J. Oncol., 15, 347 Lea, 2001, Induction of histone acetylation in mouse erythroleukemia cells by some organosulfur compounds including allyl isothiocyanate, Int. J. Cancer., 92, 784, 10.1002/ijc.1277 Lea, 2002, Induction of histone acetylation and inhibition of growth of mouse erythroleukemia cells by S-allylmercaptocysteine, Nutr. Cancer, 43, 90, 10.1207/S15327914NC431_11 Druesne, 2004, Diallyl disulfide (DADS) increases histone acetylation and p21(waf1/cip1) expression in human colon tumor cell lines, Carcinogenesis, 25, 1227, 10.1093/carcin/bgh123 Nian, 2008, Allyl mercaptan a garlic-derived organosulfur compound, inhibits histone deacetylase and enhances Sp3 binding on the P21WAF1 promoter, Carcinogenesis, 29, 1816, 10.1093/carcin/bgn165 Cheung, 2010, Molecular targets of dietary phenethyl isothiocyanate and sulforaphane for cancer chemoprevention, AAPS J., 12, 87, 10.1208/s12248-009-9162-8 Wang, 2007, Dual action on promoter demethylation and chromatin by an isothiocyanate restored GSTP1 silenced in prostate cancer, Mol. Carcinog., 46, 24, 10.1002/mc.20258 Gibellini, 2011, Quercetin and cancer chemoprevention, Evid. Based Complement Alternat Med., 2011, 591356, 10.1093/ecam/neq053 Tan, 2009, Quercetin is able to demethylate the p16INK4a gene promoter, Chemotherapy, 55, 6, 10.1159/000166383 Ruiz, 2007, Quercetin inhibits TNF-induced NF-kappaB transcription factor recruitment to proinflammatory gene promoters in murine intestinal epithelial cells, J. Nutr., 137, 1208, 10.1093/jn/137.5.1208 Lee, 2011, Quercetin induces FasL-related apoptosis, in part, through promotion of histone H3 acetylation in human leukemia HL-60 cells, Oncol. Rep., 25, 583 Priyadarsini, 2011, The flavonoid quercetin modulates the hallmark capabilities of hamster buccal pouch tumors, Nutr. Cancer., 63, 218, 10.1080/01635581.2011.523503 Ravichandran, 2014, Pharmacophore model of the quercetin binding site of the SIRT6 protein, J. Mol. Graph Model, 49, 38, 10.1016/j.jmgm.2014.01.004 Singh, 2013, Synthesis and characterization of a SIRT6 open tubular column: predicting deacetylation activity using frontal chromatography, Anal. Biochem., 436, 78, 10.1016/j.ab.2013.01.018 Kokkonen, 2014, Studying SIRT6 regulation using H3K56 based substrate and small molecules, Eur. J. Pharm. Sci., 63, 71, 10.1016/j.ejps.2014.06.015 Du, 2015, MicroRNA-143 enhances chemosensitivity of Quercetin through autophagy inhibition via target GABARAPL1 in gastric cancer cells, Biomed. Pharmacother., 74, 169, 10.1016/j.biopha.2015.08.005 Sonoki, 2015, Quercetin decreases claudin-2 expression mediated by up-Regulation of microRNA miR-16 in lung adenocarcinoma A549Cells, Nutrients, 7, 4578, 10.3390/nu7064578 Lou, 2015, The p53/miR-34a/SIRT1 positive feedback loop in quercetin induced apoptosis, Cell Physiol. Biochem., 35, 2192, 10.1159/000374024 Zhang, 2015, Quercetin enhances cisplatin sensitivity of human osteosarcoma cells by modulating microRNA-217-KRAS axis, Mol. Cells, 38, 638, 10.14348/molcells.2015.0037 Yang, 2015, Zheng JH.Combination of quercetin and hyperoside inhibits prostate cancer cell growth and metastasis via regulation of microRNA-21, Mol. Med. Rep., 11, 1085, 10.3892/mmr.2014.2813 Athar, 2009, Multiple molecular targets of resveratrol: anti- carcinogenic mechanisms, Arch. Biochem. Biophys., 486, 95, 10.1016/j.abb.2009.01.018 Savouret, 2002, Resveratrol and cancer: a review, Biomed. Pharmacother., 56, 84, 10.1016/S0753-3322(01)00158-5 Wang, 2008, Impaired DNA damage response, genome instability, and tumorigenesis in SIRT1 mutant mice, Cancer Cell, 14, 312, 10.1016/j.ccr.2008.09.001 Howitz, 2003, Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan, Nature, 425, 191, 10.1038/nature01960 Bishayee, 2009, Cancer prevention and treatment with resveratrol: from rodent studies to clinical trials, Cancer Prev. Res. (Phila), 2, 409, 10.1158/1940-6207.CAPR-08-0160 Wood, 2004, Sirtuin activators mimic caloric restriction and delay ageing in metazoans, Nature, 430, 686, 10.1038/nature02789 Boily, 2009, SirT1-null mice develop tumors at normal rates but are poorly protected by resveratrol, Oncogene, 28, 2882, 10.1038/onc.2009.147 Wang, 2008, Interplay among BRCA1, SIRT1, and survivin during BRCA1-associated tumorigenesis, Mol. Cell., 32, 11, 10.1016/j.molcel.2008.09.011 Kai, 2010, Resveratrol enhances p53 acetylation and apoptosis in prostate cancer by inhibiting MTA1/NuRD complex, Int. J. Cancer, 126, 1538 Kala, 2015, Epigenetic-based combinatorial resveratrol and pterostilbene alters DNA damage response by affecting SIRT1 and DNMT enzyme expression, including SIRT1-dependent γ-H2AX and telomerase regulation in triple-negative breast cancer, BMC Cancer, 15, 672, 10.1186/s12885-015-1693-z Wu, 2014, Shortterm resveratrol exposure causes in vitro and in vivo growth inhibition and apoptosis of bladder cancer cells, PLoS One, 9, e89806, 10.1371/journal.pone.0089806 Qin, 2014, Methylation and miRNA effects of resveratrol on mammary tumors vs normal tissue, Nutr. Cancer, 66, 270, 10.1080/01635581.2014.868910 Papoutsis, 2015, Gestational exposure to the AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin induces BRCA-1 promoter hypermethylation and reduces BRCA-1 expression in mammary tissue of rat offspring:Preventive effects of resveratrol, Mol. Carcinog., 54, 261, 10.1002/mc.22095 Azimi, 2015, Time – and concentration – dependent effects of resveratrol on miR 15a and miR16-1Expression and apoptosis in the CCRF-CEM acute lymphoblastic leukemia cell line, Asian Pac. J. Cancer Prev., 16, 6463, 10.7314/APJCP.2015.16.15.6463 Dhar, 2015, Resveratrol and pterostilbene epigenetically restore PTEN expression by targeting oncomiRs of the miR-17 family in prostate cancer, Oncotarget, 6, 27214, 10.18632/oncotarget.4877 Clarke, 2008, Multi-targeted prevention of cancer by sulforaphane, Cancer Lett., 269, 291, 10.1016/j.canlet.2008.04.018 Tomczyk, 2010, Sulforaphane–a possible agent in prevention and therapy of cancer, Postepy Hig. Med. Dosw., 64, 590 Traka, 2005, Transcriptome analysis of human colon Caco-2 cells exposed to sulforaphane, J. Nutr., 135, 1865, 10.1093/jn/135.8.1865 Meeran, 2010, Sulforaphane causes epigenetic repression of hTERT expression in human breast cancer cell lines, PLoS One, 5, e11457, 10.1371/journal.pone.0011457 Myzak, 2004, A novel mechanism of chemoprotection by sulforaphane: inhibition of histone deacetylase, Cancer Res., 64, 5767, 10.1158/0008-5472.CAN-04-1326 Myzak, 2006, Sulforaphane inhibits histone deacetylase activity in BpH −1, LnCaP and PC-3 prostate epithelial cells, Carcinogenesis, 27, 811, 10.1093/carcin/bgi265 Pledgie-Tracy, 2007, Sulforaphane induces cell type-specific apoptosis in human breast cancer cell lines, Mol. Cancer Ther., 6, 1013, 10.1158/1535-7163.MCT-06-0494 Wong, 2014, Andres Houseman E, et al Effects of sulforaphane and 3,3′-diindolylmethane on genome-wide promoter methylation in normal prostate epithelial cells and prostate cancer cells, PLoS One, 9, e86787, 10.1371/journal.pone.0086787 Su, 2014, Requirement and epigenetics reprogramming of Nrf2 in suppression of tumor promoter TPA-induced mouse skin cell transformation by sulforaphane, Cancer Prev. Res., 7, 319, 10.1158/1940-6207.CAPR-13-0313-T Mileo, 2016, Polyphenols as modulator of oxidative stress in cancer disease: new therapeutic strategies, Oxid. Med. Cell. Longevity, 2016, 6475624, 10.1155/2016/6475624 Myzak, 2006, Sulforaphane inhibits histone deacetylase in vivo and suppresses tumorigenesis in Apc-minus mice, FASEB J., 20, 506, 10.1096/fj.05-4785fje Myzak, 2007, Sulforaphane retards the growth of human PC-3 xenografts and inhibits HDAC activity in human subjects, Exp. Biol. Med. (Maywood), 232, 227 Lee, 2005, Mechanisms for the inhibition of DNA methyltransferases by tea catechins and bioflavonoids, Mol. Pharmacol., 68, 1018, 10.1124/mol.104.008367 Huang, 2008, EGCG stabilizes p27kip1 in E2-stimulated MCF-7 cells through down-regulation of the Skp2 protein, Endocrinology, 149, 5972, 10.1210/en.2008-0408 Berletch, 2008, Epigenetic and genetic mechanisms contribute to telomerase inhibition by EGCG, J. Cell Biochem., 103, 509, 10.1002/jcb.21417 Navarro-Peran, 2007, Effects of folate cycle disruption by the green tea polyphenol epigallocatechin-3-gallate, Int. J. Biochem. Cell Biol., 39, 2215, 10.1016/j.biocel.2007.06.005 Kato, 2008, Effects of green tea polyphenol on methylation status of RECK gene and cancer cell invasion in oral squamous cell carcinoma cells, Br. J. Cancer., 99, 647, 10.1038/sj.bjc.6604521 Tang, 2008, Persistent hypomethylation in the promoter of nucleosomal binding protein 1 (Nsbp1) correlates with overexpression of Nsbp1 in mouse uteri neonatally exposed to diethylstilbestrol or genistein, Endocrinology, 149, 5922, 10.1210/en.2008-0682 Fang, 2005, Promoter hypermethylation and inactivation of O(6)-methylguanine-DNA methyltransferase in esophageal squamous cell carcinomas and its reactivation in cell lines, Int. J. Oncol., 26, 615 Vandegehuchte, 2010, Direct and transgenerational impact on Daphnia magna of chemicals with a known effect on DNA methylation, Comp. Biochem. Physiol. C Toxicol. Pharmacol., 151, 278, 10.1016/j.cbpc.2009.11.007 Paluszczak, 2010, The effect of dietary polyphenols on the epigenetic regulation of gene expression in MCF7 breast cancer cells, Toxicol. Lett., 192, 119, 10.1016/j.toxlet.2009.10.010 Stefanska, 2010, Hypomethylation and induction of retinoic acid receptor beta 2 by concurrent action of adenosine analogues and natural compounds in breast cancer cells, Eur. J. Pharmacol., 638, 47, 10.1016/j.ejphar.2010.04.032 Singh, 2009, Computational screening of molecular targets in Plasmodium for novel non-resistant anti-malarial drugs, Bioinformation, 3, 255, 10.6026/97320630003255 Kang, 2005, Curcumin-induced histone hypoacetylation: the role of reactive oxygen species, Biochem. Pharmacol., 69, 1205, 10.1016/j.bcp.2005.01.014 Cui, 2007, PfGCN5-mediated histone H3 acetylation plays a key role in gene expression in Plasmodium falciparum, Eukaryot. Cell, 6, 1219, 10.1128/EC.00062-07 Sng, 2006, Histone modifications in kainate-induced status epilepticus, Eur. J. Neurosci., 23, 1269, 10.1111/j.1460-9568.2006.04641.x Chiu, 2009, Curcumin prevents diabetes-associated abnormalities in the kidneys by inhibiting p300 and nuclear factor-kappaB, Nutrition, 25, 964, 10.1016/j.nut.2008.12.007 Tikoo, 2008, Change in post-translational modifications of histone H3, heat-shock protein-27 and MAP kinase p38 expression by curcumin in streptozotocin-induced type I diabetic nephropathy, Br. J. Pharmacol., 153, 1225, 10.1038/sj.bjp.0707666 Li, 2008, Curcumin prevents and reverses murine cardiac hypertrophy, J. Clin. Invest., 118, 879 Morimoto, 2008, The dietary compound curcumin inhibits p300 histone acetyltransferase activity and prevents heart failure in rats, J. Clin. Invest., 118, 868 Liu, 2005, Curcumin a potent anti-tumor reagent, is a novel histone deacetylase inhibitor regulating B-NHL cell line Raji proliferation, Acta Pharmacol. Sin., 26, 603, 10.1111/j.1745-7254.2005.00081.x Choi, 2009, Epigallocatechin-3-gallate, a histone acetyltransferase inhibitor, inhibits EBV-induced B lymphocyte transformation via suppression of RelA acetylation, Cancer Res., 69, 583, 10.1158/0008-5472.CAN-08-2442 Lea, 2001, Induction of histone acetylation in rat liver and hepatoma by organosulfur compounds including diallyl disulfide, Anticancer Res., 21, 2841 Schwab, 2008, The dietary histone deacetylase inhibitor sulforaphane induces human beta-defensin-2 in intestinal epithelial cells, Immunology, 125, 241, 10.1111/j.1365-2567.2008.02834.x Hu, 2006, Cancer chemoprevention of intestinal polyposis in ApcMin/+ mice by sulforaphane, a natural product derived from cruciferous vegetable, Carcinogenesis, 27, 2038, 10.1093/carcin/bgl049 Pledgie-Tracy, 2007, Sulforaphane induces cell type-specific apoptosis in human breast cancer cell lines, Mol. Cancer Ther., 6, 1013, 10.1158/1535-7163.MCT-06-0494 Chakrabarti, 2012, Alterations in expression of specific microRNAs by combination of 4-HPR and EGCG inhibited growth of human malignant neuroblastoma cells, Brain Res., 1454, 1, 10.1016/j.brainres.2012.03.017 Chakrabarti, 2013, miR-138 overexpression is more powerful than hTERT knockdown to potentiate apigenin for apoptosis in neuroblastoma in vitro and in vivo, Exp. Cell Res., 319, 1575, 10.1016/j.yexcr.2013.02.025 Jiang, 2011, MicroRNA HSA-miR-125a-5p induces apoptosis by activating p53 in lung cancer cells, Exp. Lung Res., 37, 387, 10.3109/01902148.2010.492068 Saini, 2011, Curcumin modulates microRNA-203-mediated regulation of the Src-Akt axis in bladder cancer, Cancer Prev. Res. (Phila.), 4, 1698, 10.1158/1940-6207.CAPR-11-0267 Zhang, 2010, Curcumin promotes apoptosis in human lung adenocarcinoma cells through miR-186n signaling pathway, Oncol. Rep., 24, 1217, 10.3892/or_00000975 Gao, 2012, Pure curcumin decreases the expression of WT1 by upregulation of miR-15a and miR-16-1 in leukemic cells, J. Exp. Clin. Cancer Res., 31, 27, 10.1186/1756-9966-31-27 Sun, 2008, Curcumin (diferuloylmethane) alters the expression profiles of microRNAs in human pancreatic cancer cells, Mol. Cancer Ther., 7, 464, 10.1158/1535-7163.MCT-07-2272 Tsang, 2010, Epigallocatechin gallate up-regulation of miR-16 and induction of apoptosis in human cancer cells, J. Nutr. Biochem., 21, 140, 10.1016/j.jnutbio.2008.12.003 Gandhy, 2012, Curcumin and synthetic analogs induce reactive oxygen species and decreases specificity protein (Sp) transcription factors by targeting microRNAs, BMC Cancer, 12, 564, 10.1186/1471-2407-12-564 Jin, 2011, 3,3′-Diindolylmethane inhibits breast cancer cell growth via miR-21-mediated Cdc25A degradation, Mol. Cell Biochem., 358, 345, 10.1007/s11010-011-0985-0 Kong, 2012, Epigenetic silencing of miR-34a in human prostate cancer cells and tumor tissue specimens can be reversed by BR-DIM treatment, Am. J. Transl. Res., 4, 14 Melkamu, 2010, Alteration of microRNA expression in vinyl carbamate-induced mouse lung tumors and modulation by the chemopreventive agent indole-3-carbinol, Carcinogenesis, 31, 252, 10.1093/carcin/bgp208 Ahn, 2012, Lycopene inhibits hepatic steatosis via microRNA-21-induced downregulation of fatty acid-binding protein 7 in mice fed a high-fat diet, Mol. Nutr. Food Res., 56, 1665, 10.1002/mnfr.201200182 Chiang, 2013, Organosulfur garlic compounds induce neovasculogenesis in human endothelial progenitor cells through a modulation of MicroRNA 221 and the PI3-K/Akt signaling pathways, J. Agric. Food Chem., 61, 4839, 10.1021/jf304951p Xiao, 2014, Diallyl disulfide suppresses SRC/Ras/ERK signaling-mediated proliferation and metastasis in human breast cancer by up-regulating miR-34a, PLoS One, 9, e112720, 10.1371/journal.pone.0112720 Dhar, 2011, Resveratrol and prostate cancer: promising role for microRNAs, Mol. Nutr. Food Res., 55, 1219, 10.1002/mnfr.201100141 Sheth, 2012, Resveratrol reduces prostate cancer growth and metastasis by inhibiting the Akt/MicroRNA-21 pathway, PLoS One, 7, e51655, 10.1371/journal.pone.0051655 Tili, 2010, Resveratrol modulates the levels of microRNAs targeting genes encoding tumor-suppressors and effectors of TGFbeta signaling pathway in SW480 cells, Biochem. Pharmacol., 80, 2057, 10.1016/j.bcp.2010.07.003 Sakurai, 2014, Gefitinib and luteolin cause growth arrest of human prostate cancer PC-3 cells via inhibition of cyclin G-associated kinase and induction of miR-630, PLoS One, 9, e100124, 10.1371/journal.pone.0100124 Wu, 2015, Luteolin induces apoptosis by up-regulating miR-34a in human gastric cancer cells, Technol. Cancer Res. Treat., 14, 747, 10.7785/tcrt.2012.500434 Xiao, 2012, miR-141modulates androgen receptor transcriptional activity in human prostate cancer cells through targeting the small heterodimer partner protein, Prostate, 72, 1514, 10.1002/pros.22501 Ide, 2010, Combined inhibitory effects of soy isoflavones and curcumin on the production of prostate-specific antigen, Prostate, 70, 1127, 10.1002/pros.21147 Sharma, 2001, Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in patients with colorectal cancer, Clin. Cancer Res., 7, 1894 Johnson, 2010, Green tea polyphenols for prostate cancer chemoprevention: a translational perspective, Phytomedicine, 17, 3, 10.1016/j.phymed.2009.09.011 Nguyen, 2012, Randomized, double-blind, placebo-controlled trial of polyphenon E in prostate cancer patients before prostatectomy: evaluation of potential chemopreventive activities, Cancer Prev. Res., 5, 290, 10.1158/1940-6207.CAPR-11-0306 Lazarevic, 2012, The effects of short-term genistein intervention on prostate biomarker expression in patients with localised prostate cancer before radical prostatectomy, Br. J. Nutr., 108, 2138, 10.1017/S0007114512000384 Miyanaga, 2012, Prostate cancer chemoprevention study: an investigative randomized control study using purified isoflavones in men with rising prostate-specific antigen, Cancer Sci., 103, 125, 10.1111/j.1349-7006.2011.02120.x Heath, 2010, A phase I dose-escalation study of oral BR-DIM in castrate-resistant, non-metastatic prostate cancer, Am. J. Transl. Res., 2, 402 Mariani, 2014, Low prostate concentration of lycopene is associated with development of prostate cancer in patients with high-grade prostatic intraepithelial neoplasia, Int. J. Mol. Sci., 15, 1433, 10.3390/ijms15011433 Goldberg, 2003, Absorption of three wine-related polyphenols in three different matrices by healthy subjects, Clin. Biochem., 36, 79, 10.1016/S0009-9120(02)00397-1 Alumkal, 2015, A phase II study of sulforaphane-rich broccoli sprout extracts in men with recurrent prostate cancer, Investig. New Drugs, 33, 480, 10.1007/s10637-014-0189-z