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Dietary Phytochemicals as Epigenetic Modulators in Cancer

  • Vijay S. Thakur
  • Sanjay Gupta
Chapter

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.

Keywords

HDAC Activity Organosulfur Compound Resveratrol Treatment hTERT Promoter EGCG Treatment 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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

Notes

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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© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  1. 1.Department of Urology & NutritionCase Western Reserve UniversityClevelandUSA
  2. 2.University Hospitals Case Medical CenterClevelandUSA
  3. 3.Case Comprehensive Cancer CenterClevelandUSA

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