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Garlic: Allyl Sulfur Compounds and Cancer Prevention

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Nutraceuticals and Cancer Signaling

Part of the book series: Food Bioactive Ingredients ((FBC))

Abstract

Garlic, Allium sativum L., is a plant within the family Alliaceae that has been widely used for its culinary and medicinal properties. This plant contains organosulfur compounds with allyl groups such as allyl mercaptan (AM), S-allyl cysteine (SAC), diallyl trisulfide (DATS) and has been responsible for different health benefits such as antihypertensive, anticoagulant, anti-inflammatory, antimicrobial and anticancer. Especially some lipid-soluble allyl sulfur compounds can inactivate carcinogens and reduce cancer risk and regulate the cellular processes. Epidemiological studies have shown that garlic and its components can decrease the incidence of human stomach, colon, prostate, brain, skin, breast, lung, uterine, and esophagus cancers. These anticarcinogenic effects appear to be achieved by modifying common signaling pathways. But allyl sulfur compounds have different effect in supressing tumor proliferation. Therefore, the compounds that are responsible for the cellular and molecular effects, the stages which they suppress neoplasia and interactions with other drugs should be very well known. Tumor supression ability of allyl sulfur compounds of garlic is attributed the stimulation of detoxification enzymes, protection from oxidative stress, induction of cell apoptosis and cell cycle arrest, prevention of chromosomal damage, induction of immune system and supression of nitrosamine bioactivation. On the other hand, not only the genetic mechanisms, but also the epigenetic mechanisms can be associated with the cancer prevention. Garlic and its several allyl sulfur compounds can be modified by both DNA methylation and histon acetylation. In this chapter, preclinical and clinical studies on the effects of garlic consumption in reducing cancer prevalence will be presented in detail. Furthermore, studies involving the use of allyl sulfur compounds individually or in combination will be discussed and their mechanisms of action will be interpreted at cellular and molecular level.

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Abbreviations

AGE:

Aged garlic extract

AM:

Allyl mercaptan

AMD:

Allyl methyl disulfide

AMPK/TSC2:

AMP-activated protein kinase/tuberous sclerosis complex

AMS:

Allyl methyl sulfide

Bak:

Bcl-2 homologous antagonist killer

Bax:

Bcl-2-associated X protein

Bcl-2:

B-cell lymphoma 2

Bcl-xL:

B-cell lymphoma-extra large

Bip:

Binding immunoglobulin protein

BP:

Benzo[a]pyrene

Cdc2:

Cell division cycle-2

Cdc25:

Cell division cycle-25

Cdk:

Cyclin dependent kinases

CHOP:

CCAAT-enhancer-binding protein homologous protein

DADS:

Diallyl disulfide

DAS:

Diallyl sulfide

DATS:

Diallyl trisulfide

DATTS:

Dialyl tetrasulfide

DMBA:

7,12-Dimethylbenz[a]anthracene

DMH:

1,2-Dimethylhydrazine

DNA:

Deoxyribonucleic acid

DNMTi:

DNA methyltransferase inhibitors

DNMTs:

DNA methyltransferases

eIF2α:

Eukaryotic translation initiation factor 2α

EMT:

Epithelial-mesenchymal transition

ER:

Endoplasmic retikulum

ERK1/2:

Extracellular signal–regulated kinases1/2

FAK:

Focal adhesion kinase

FOXM1:

Forkhead box protein M1

GADD153:

G1 arrest and DNA damage 153

GPx:

Glutathione peroxidase

GRP78:

Glucose-regulated protein78

GSH:

Glutathione

GSK-3β:

Glycogen synthase kinase 3β

GST:

Glutathione-S-transferase

H2O2:

Hydrogen peroxide

H2S:

Hydrogen sulfide

HCC:

Hepatocellular carcinoma

HDAC:

Histone deacetylase

HER2:

Human epidermal growth factor receptor2

H-RAS:

Harvey rat sarcoma viral oncogene homolog

IFNγ:

Interferon-gamma

IL10:

Interleukin 10

IL12:

Interleukin 12

IL1α:

Interleukin 1α

IL1β:

Interleukin 1β

IL2:

Interleukin 2

IL6:

Interleukin 6

IL8:

Interleukin 8

JNK:

c-Jun terminal kinase

LPS:

Lipopolysaccharide

MAPK:

Mitogen-activated protein kinase

MEK:

MAPK/ERK kinase

MMP:

Matrix metallopeptidases

NF-κB:

Nuclear factor kappa light chain enhancer of activated B cells

NO:

Nitric oxide

NQO:

NAD(P)H:quinone acceptor oxidoreductase

Nrf2:

Nuclear factor erythroid 2-related factor 2

OSCs:

Organosulfur compounds

P13k/Akt/mTOR:

Phosphoinositide-3-kinase/protein kinase B

p38 MAPK:

p38 mitogen-activated protein kinases

PCNA:

Proliferation cell nuclear antigen

PUMA:

p53 upregulated modulator of apoptosis

ROS:

Reactive oxygen species

SAC:

S-allyl cysteine

SAMC:

S-allylmercaptocysteine

Slug (SNAI2):

Snail family transcriptional repressor 2

SOD:

Superoxide dismutase

TGF-β:

Transforming growth factor beta 1

TLRs:

Toll-like receptors

TNF-α:

Tumor necrosis factor-α

TPA:

12-O-tetradecanoylphorbol-13-acetate

UGT:

UDP-glucuronosyl transferase

UPR:

Unfolded protein response

VEGF:

Vascular endothelial growth factor

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  1. Biotechnology Research Center of Ministry of Agriculture and Forestry, Yenimahalle, Ankara, Turkey

    Sumeyra Cetinkaya

  2. Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, Etiler, Ankara, Turkey

    Ipek Süntar

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  1. Sumeyra Cetinkaya
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  1. Food Materials & Process Design Eng, Gorgan University of Agricultural Sciences and Natural Resources, Gorgan, Iran

    Seid Mahdi Jafari

  2. Baqiyatallah University of Medical Sciences, Tehran, Iran

    Seyed Mohammad Nabavi

  3. National Institute of Agrarian and Veterinary Research (INIAV), Vila do Conde, Portugal

    Ana Sanches Silva

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Cetinkaya, S., Süntar, I. (2021). Garlic: Allyl Sulfur Compounds and Cancer Prevention. In: Jafari, S.M., Nabavi, S.M., Silva, A.S. (eds) Nutraceuticals and Cancer Signaling. Food Bioactive Ingredients. Springer, Cham. https://doi.org/10.1007/978-3-030-74035-1_11

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