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Dietary Phytochemicals as Epigenetic Modulators in Cancer

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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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Authors and Affiliations

  1. Department of Urology & Nutrition, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH, 44106, USA

    Vijay S. Thakur Ph.D. & Sanjay Gupta Ph.D.

  2. University Hospitals Case Medical Center, 11100 Euclid Avenue, Cleveland, OH, USA

    Vijay S. Thakur Ph.D. & Sanjay Gupta Ph.D.

  3. Case Comprehensive Cancer Center, Cleveland, OH, 44106, USA

    Sanjay Gupta Ph.D.

Authors
  1. Vijay S. Thakur Ph.D.
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  2. Sanjay Gupta Ph.D.
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Correspondence to Sanjay Gupta Ph.D. .

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Editors and Affiliations

  1. , Pathology and Laboratory Medicine, University of Kansas Medical Center, Rainbow Blvd 3901, Kansas City, 66160, Kansas, USA

    Sharmila Shankar

  2. , Pharmacology and Toxicology, University of Kansas Medical Center, Rainbow Blvd 3901, Kansas City, 66160, Kansas, USA

    Rakesh K. Srivastava

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© 2012 Springer Science+Business Media B.V.

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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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