Abstract
Epigenetics refers to heritable changes in gene expression that are not attributable to changes in DNA sequence, but rather depend on alterations in DNA methylation, chromatin structure or microRNA profiles. Although epigenetic changes are heritable in somatic cells, these modifications are potentially reversible and make them attractive and promising targets in the prevention and therapy of cancer. Dietary phytochemicals, especially present in fruits, vegetables and beverages have recently shown considerable promise in affecting gene expression via reversible epigenetic mechanisms. These agents include tea polyphenols, genistein, curcumin, sulforaphane, isothiocynates, lycopene, resveratrol, quercetin, indol-3-carbinol, ellagitannin and organosulfur compounds. This chapter discusses the impact of environment, lifestyle and dietary factors on epigenetic alterations and presents considerable evidence that modulation of epigenetic targets by dietary phytochemicals is associated with the prevention and therapy of cancer. This chapter also emphasizes that an increased understanding of the anticancer effects of dietary phytochemicals offer new epigenetic targets and promising agents with more opportunities for prevention, and perhaps therapy of cancer.
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Abbreviations
- Akt:
-
v-akt murine thymoma viral oncogene homolog 1
- AM:
-
allyl mercaptan
- AP-1:
-
Activator Protein-1
- AR:
-
androgen receptor
- Bax:
-
BCL2-associated X protein
- Bcl2:
-
B-cell CLL/lymphoma 2
- Bcl-xL:
-
B-cell lymphoma-extra large
- Bmi-1:
-
B-cell-specific Moloney murine leukemia virus integration site 1
- BRCA1:
-
breast cancer 1 early onset
- CBP:
-
CREB-binding protein
- CCND2:
-
cyclin D2
- Cdc25A:
-
cell division cycle 25 homolog A
- Cdk:
-
cyclin-dependent kinase
- CDX-2:
-
caudal-related homeodomain protein 2
- c-Kit:
-
v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog
- COMT:
-
catechol-O-methyltransferase
- COX-2:
-
cyclooxygenase-2
- CYLD:
-
cylindromatosis (turban tumor syndrome)
- DADS:
-
diallyl disulfide
- DAS:
-
diallyl sulfide
- DATS:
-
diallyl trisulfide
- DHFR:
-
dihydrofolate reductase
- DMBA:
-
7,12-dimethylbenz(a)anthracene
- DNMT:
-
DNA methyltransferase
- DNMT-3 L:
-
DNA (cytosine-5)-methyltransferase 3-like
- E2F:
-
E2F transcription factor
- EC:
-
[−]-epicatechin
- ECG:
-
[−]-epicatechin-3-gallate
- EGC:
-
[−]-epigallocatechin
- EGCG:
-
[−]-epigallocatechin-3-gallate
- EGFR:
-
epidermal growth factor receptor
- ER:
-
estrogen receptor
- ERβ:
-
estrogen receptor beta
- ERBB2:
-
human epidermal growth factor receptor 2
- ERα:
-
estrogen receptor alpha
- EZH-2:
-
enhancer of zeste homolog 2
- FOXO3a:
-
forkhead box protein O3
- GCN5:
-
SAGA complex histone acetyltransferase catalytic subunit Gcn5
- GSTP1:
-
glutathione-S-transferase pi 1
- HATs:
-
histone acetyl transferases
- HDACs:
-
histone deacetylase
- HER-2:
-
human epidermal growth factor receptor 2
- HIF-1 α:
-
hypoxia inducible factor 1 alpha subunit
- HKMTs:
-
histone lysine methyltransferases
- hMLH1:
-
human mutL homolog 1
- HOX family proteins:
-
homeobox family proteins
- HSP90:
-
heat shock protein 90
- hTERT:
-
human telomerase reverse transcriptase
- IP-10:
-
TNF-induced interferon-gamma-inducible protein 10
- K:
-
Lysine
- LEF:
-
lymphoid enhancer factor
- LOI:
-
loss of imprinting
- MBD:
-
methylated DNA binding domain proteins
- MCL1:
-
induced myeloid leukemia cell differentiation protein Mcl-1
- MCM-2:
-
minichromosome maintenance gene
- MGMT-O(6):
-
methylguanine-DNA methyltransferase
- MIP-2:
-
macrophage inflammatory protein 2
- miRNA:
-
microRNA
- MMP:
-
matrix metalloproteinase
- MTA-2:
-
metastasis associated 1 family member 2
- NF-κB:
-
nuclear factor kappa-light-chain-enhancer of activated B cells
- Notch1:
-
notch homolog 1 translocation-associated (Drosophila)
- NuRD:
-
nucleosome remodeling complex
- OSCs:
-
organosulfur compounds
- p16INK4a:
-
cyclin-dependent kinase 4 inhibitor A
- p21WAF1/CIP1:
-
cyclin-dependent kinase inhibitor 1A
- p53:
-
tumor protein 53
- PARP:
-
Poly ADP-ribose polymerase
- PCAF:
-
K(lysine) acetyltransferase 2B
- PcG:
-
polycomb group proteins
- PDCD4:
-
programmed cell death 4
- PEITC:
-
phenethyl isothiocyanate
- PRMTs:
-
arginine methyltransferases
- PRPS1:
-
phosphoribosyl pyrophosphate synthetase 1
- PTEN:
-
phosphatase and tensin homolog deleted on chromosome 10
- RARβ2:
-
retinoic acid receptor beta 2
- R:
-
Arginine
- RAS:
-
rat sarcoma transforming oncogene
- RASSF1A:
-
RAS association domain family 1A
- RECK:
-
reversion-inducing cysteine-rich protein with Kazal motifs repressive complex 3
- RXR alpha:
-
retinoid X receptor alpha
- SAH:
-
S-adenosyl-L-homocysteine
- SAM:
-
S-adenosyl methionine
- SAMC:
-
S-allylmercaptocysteine
- SIRT1:
-
sirtuin (silent mating type information regulation 2 homolog) 1
- SLC16A1:
-
solute carrier family 16 member 1
- SNX19:
-
sorting nexin-19
- SP1:
-
transcription Factor Sp1
- TCF:
-
multiple T-cell factor
- TGFBR2:
-
transforming growth factor beta receptor II
- TGF-β:
-
transforming growth factor beta
- TIMP-2:
-
tissue inhibitor of metalloproteinase 2
- TTK:
-
phosphotyrosine picked threonine-protein kinase
- VEGF:
-
vascular endothelial cell growth factor
- ZBTB10:
-
zinc finger and BTB domain containing 10
- ZEB1:
-
zinc finger E-box binding homeobox 1
- ZNF513:
-
zinc finger protein 513
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Acknowledgements
The original work from author’s laboratory outlined in this review was supported by United States Public Health Service Grants RO1CA108512, RO1CA115491 and RO1AT002709. We apologize to those investigators whose original work could not be cited owing to the space limitations.
Conflict of interest : The authors have no competing interest
Dr Sanjay Gupta is Carter Kissell Associate Professor & Research Director in the Department of Urology and holds secondary appointment in the Department of Nutrition at Case Western Reserve University and Division of General Medical Sciences at Case Comprehensive Cancer Center, Cleveland, Ohio, USA.
Dr Vijay S Thakur is Senior Research Associate in the Department of Urology at Case Western Reserve University, Cleveland, Ohio, USA.
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Thakur, V.S., Gupta, S. (2012). Dietary Phytochemicals as Epigenetic Modulators in Cancer. In: Shankar, S., Srivastava, R. (eds) Nutrition, Diet and Cancer. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2923-0_19
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