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Dietary phytochemicals alter epigenetic events and signaling pathways for inhibition of metastasis cascade

Phytoblockers of metastasis cascade

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Abstract

Cancer metastasis is a multistep process in which a cancer cell spreads from the site of the primary lesion, passes through the circulatory system, and establishes a secondary tumor at a new nonadjacent organ or part. Inhibition of cancer progression by dietary phytochemicals (DPs) offers significant promise for reducing the incidence and mortality of cancer. Consumption of DPs in the diet has been linked to a decrease in the rate of metastatic cancer in a number of preclinical animal models and human epidemiological studies. DPs have been reported to modulate the numerous biological events including epigenetic events (noncoding micro-RNAs, histone modification, and DNA methylation) and multiple signaling transduction pathways (Wnt/β-catenin, Notch, Sonic hedgehog, COX-2, EGFR, MAPK-ERK, JAK-STAT, Akt/PI3K/mTOR, NF-κB, AP-1, etc.), which can play a key role in regulation of metastasis cascade. Extensive studies have also been performed to determine the molecular mechanisms underlying antimetastatic activity of DPs, with results indicating that these DPs have significant inhibitory activity at nearly every step of the metastatic cascade. DPs have anticancer effects by inducing apoptosis and by inhibiting cell growth, migration, invasion, and angiogenesis. Growing evidence has also shown that these natural agents potentiate the efficacy of chemotherapy and radiotherapy through the regulation of multiple signaling pathways. In this review, we discuss the variety of molecular mechanisms by which DPs regulate metastatic cascade and highlight the potentials of these DPs as promising therapeutic inhibitors of cancer.

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Abbreviations

ABCG2:

ATP-binding cassette sub-family G member 2

ACSL1:

Acyl-CoA synthetase long-chain family member 1

AKBA:

Acetyl-11-keto-β-boswellic acid

ALDH:

Aldehyde dehydrogenase

AP-1:

Activator protein-1

APC:

Adenomatous polyposis coli

BAFF:

B cell activating factor of the TNF family

Bcl-2:

B cell lymphoma-2

BTG3:

B cell translocation gene 3

CCND2:

Cyclin D2

Cdk:

Cyclin-dependent kinase

COX-2:

Cyclooxygenase-2

CSCs:

Cancer stem cells

DNMT:

DNA methyltransferase

DRs:

Death receptors

EGCG:

Epigallocatechin-3-gallate

EMT:

Epithelial–mesenchymal transition

ERK:

Extracellular signal-regulated kinase

FOXO:

Forkhead box O

GSK3β:

Glycogen synthase kinase 3 beta

GSTP1:

Glutathione S-transferase pi 1

GTPs:

Green tea polyphenols

HAT:

Histone acetyltransferase

HDAC:

Histone deacetyltransferase

HER2:

Human epidermal growth factor receptor 2

Hh:

Sonic hedgehog

hMLH1:

Human mutL homologue 1

hTERT:

Human telomerase reverse transcriptase

I3C:

Indole-3-carbinol

ICAM-1:

Intercellular adhesion molecule-1

IkBα:

Inhibitory kappa B alpha

IKK:

IkBα kinase

IL:

Interleukin

iNOS:

Inducible nitric oxide synthase

IRAK-1:

IL-1 receptor-associated kinase 1

JAK/STAT:

Janus kinase/signal transducers and activators of transcription

JNK:

c Jun N-terminal kinase

LDH:

Lactate dehydrogenase

LOX:

Lipoxygenase

LPS:

Lipopolysaccharide

MAPK:

Mitogen-activated protein kinases

MBD2:

Methyl-CpG binding domain protein 2

MGMT:

Methyl guanine methyl transferase

miRs:

Micro-RNAs

MMP:

Matrix metalloproteinase

MTA-2:

Metastasis-associated protein 2

mTOR:

Mammalian target of rapamycin

NF-AT:

Nuclear factor of activated T cells

NF-κB:

Nuclear factor-kappa B

NIK:

NF-κB-inducing kinase

PARP:

Polyadenosine-5′-diphosphate-ribose polymerase

PDGF:

Platelet-derived growth factor

PDK:

Pyruvate dehydrogenase kinase

PGE2 :

Prostaglandin E2

PI3K:

Phosphoinositide 3-kinase

PITCH:

Phenyl isothiocyanate

PTEN:

Phosphatase and tensin homolog

RARβ:

Retinoic acid receptor β

SFN:

Sulforaphane

TGF:

Transforming growth factor

TNF:

Tumor necrosis factor

TPA:

Phorbol 12-O-tetradecanoate-13-acetate

TRAMP:

Transgenic adenocarcinoma of mouse prostate

TSGs:

Tumor suppressor genes

UVB:

Ultraviolet B

VEGF:

Vascular endothelial growth factor

ZEB1:

Zinc finger E-box binding homeobox 1

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Acknowledgments

The Centre of Excellence in Materials Science (Nanomaterials), Department of Applied Physics, Z.H. College of Engineering & Technology, Aligarh Muslim University, Aligarh-202 002, Uttar Pradesh, India is greatly acknowledged.

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Singh, B.N., Singh, H.B., Singh, A. et al. Dietary phytochemicals alter epigenetic events and signaling pathways for inhibition of metastasis cascade. Cancer Metastasis Rev 33, 41–85 (2014). https://doi.org/10.1007/s10555-013-9457-1

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