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Genetic and epigenetic cancer chemoprevention on molecular targets during multistage carcinogenesis

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Abstract

The main goal of cancer chemoprevention is to prevent or halt the progression of carcinogenesis with the administration of synthetic or natural compounds. Fundamental chemopreventive strategies include inhibition of genetic damage, anti-proliferation/cell cycle regulation, and induction of apoptosis and anti-inflammatory processes, which may be critical for carcinogenesis intervention. Recently, a new paradigm for identifying chemopreventive agents has been implemented. It focuses on defining new biomarkers that can be used to evaluate chemopreventive efficacy based on multistage carcinogenesis. The functional roles of chemopreventive agents are associated with the modulation of nuclear factor kappa B, nuclear factor erythroid 2-related factor, p53, AMPK/mTOR, phosphatidylinositol 3-kinase, epidermal growth factor receptor, cyclooxygenase-2, chemokine (C-X-C motif) receptor 2, and sphingosine-1-phosphate. This paper summarizes the genetic and epigenetic effects of chemopreventive agents on the expression of cancer-related target genes mediated by epigenetic alterations, such as DNA methylation and histone modifications. This review will provide unique and effective strategies for reducing cancer and aging-related diseases in humans.

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Abbreviations

AhR:

Aryl hydrocarbon receptor

AhR:

Aryl hydrocarbon receptor

AMPK:

5′-AMP-activated protein kinase

AP-1:

Activator protein 1

B[a]P:

Benzo[a]pyrene

CAR:

Constitutive androstane receptor

CDK:

Cyclin-dependent kinase

CDK:

Cyclin-dependent kinase

COX-2:

Cyclooxygenase-2

CRC:

Colorectal cancer

CXCR2:

Chemokine (C-X-C motif) receptor 2

DAPK:

Death-associated protein kinase

DBP:

Dibenzo[a,l]pyrene

DCF:

Diclofenac

DNMT:

DNA methyltransferase

DRAM:

Damage-regulated autophagy modulator

EGF:

Epidermal growth factor

EGCG:

Epigallocatechin gallate

EGFR:

Epidermal growth factor receptor

ER:

Estrogen receptor

ERK:

Extracellular signal-regulated kinase

FAP:

Familial adenomatous polyposis

G-CSF:

Granulocyte colony-stimulating factor

GST:

Glutathione-S-transferase

HATs:

Histone acetyltransferases

HDACs:

Histone deacetylases

5-HETE:

5-Hydroxyeicosatetraenoic acid

hMLH1:

Human mutL homologue 1

I3C:

Indole-3-carbinol

IGF:

Insulin-like growth factor

IGFBP3:

IGF-binding protein 3

LPS:

Lipopolysaccharide

MGMT:

O 6-Methylguanine methyltransferase

MMPs:

Matrix metalloproteinases

NAC:

N-Acetylcysteine

NF-κB:

Nuclear factor kappa-light-chain-enhancer of activated B cells

Nrf2:

Nuclear factor erythroid 2-related factor 2

NSAIDs:

Nonsteroidal anti-inflammatory drugs

NQO1:

NAD(P)H:quinone oxidoreductase 1

iNOS:

Inducible nitric oxide synthase

PI3K:

Phosphatidylinositol-3-kinases

PKC:

Protein kinase C

PR:

Progesterone receptor

PPAR:

Peroxisome proliferator-activated receptors

PSA:

Prostate-specific antigen

PsA:

Psammaplin A

PXR:

Pregnane X receptor

PXR:

Pregnane X receptor

RACK:

Receptor for activated C kinase

RARβ:

Retinoic acid receptor β

ROS:

Reactive oxygen species

RNS:

Reactive nitrogen species

RASSF1A:

Ras association domain family protein 1A

SFN:

Sulforaphane

SIRT:

Silent mating type information regulation 2 homolog

SOD:

Superoxide dismutase

S1P:

Sphingosine-1-phosphate

TCDD:

2,3,7,8-Tetrachlorodibenzo-p-dioxin

TIMP-1:

Tissue inhibitor of metalloproteinase-1

TRAIL:

TNF-related apoptosis-inducing ligand

VtD:

Vitamin D

VDR:

Vitamin D receptor

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Acknowledgments

This research was supported by a Grant R0003962 from the Ministry of Trade, Industry & Energy (MOTIE), Korea Institute for Advancement of Technology (KIAT) through the Encouragement Program for the Industries of Economic Cooperation Region, and National Research Foundation of Korea (NRF) Grants funded by the Korean Government (NRF-2016R1A2B2011071 and NRF-2016R1A4A1011189).

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  1. Division of Toxicology, College of Pharmacy, Sungkyunkwan University, Seoburo 2066, Suwon, Gyeonggi-Do, 440-746, Republic of Korea

    Hyung Sik Kim & Byung Mu Lee

  2. McLaughlin Centre for Population Health Risk Assessment, University of Ottawa, Ottawa, ON, Canada

    Sam Kacew

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Kim, H.S., Kacew, S. & Lee, B.M. Genetic and epigenetic cancer chemoprevention on molecular targets during multistage carcinogenesis. Arch Toxicol 90, 2389–2404 (2016). https://doi.org/10.1007/s00204-016-1813-9

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