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Modulation of hydrogen sulfide gasotransmitter limits the proven benefits of garlic

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Abstract

Garlic has been used as a medicinal food for centuries. The biological activity of garlic relies on the presence of highly reactive sulfur compounds. Widespread in vitro and in vivo studies have reported the mechanism of action of the anticancer activity of garlic-derived organosulfur compounds (OSCs) in a wide range of cancer types. Moreover, epidemiological studies support an inverse correlation between garlic intake and cancer risk. More recently, several studies have reported the ability of garlic-derived OSCs to release hydrogen sulfide (H2S) and to affect H2S biosynthesis by altering specific H2S enzyme activity, such as cystathionine-beta-synthase or cystathionine-gamma-lyase. Paradoxically, some studies have reported that overexpression of H2S-producing enzymes is associated with ovarian and colon cancer progression. In this review, we aimed to provide a critical analysis of garlic anticancer activity by documenting our current understanding of the anticancer activity of garlic-derived OSCs. We propose here to raise a mechanistic gap in garlic-mediated anticancer activity by documenting our current knowledge of the role of H2S in cancer biology.

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Abbreviations

3-MST:

3-Mercaptopyruvate Sulfurtransferase

AGE:

Aged garlic extracts

AM:

Allyl Mercaptan

AMS:

Allyl Methyl sulfide

AMSO:

Allyl Methyl Sulfoxide

AMSO2:

Allyl Methyl Sulfone

AOAA:

Aminooxyacetic Acid

Bax:

Bcl-2-associated X protein

Bcl-2:

B-cell lymphoma 2

Bid:

BH3 interacting domain death agonist

CAT:

Cysteine Aminotransferase

CBS:

Cystathionine-beta-synthase

CSE:

Cystathionine-gamma-lyase

Cys:

Cysteine

DADS:

Diallyl Disulfide

DAS:

Diallyl Sulfide

DATS:

Diallyl Trisulfide

DATTS:

Diallyl Tetrasulfide

DBTTS:

Dibenzyl Tetrasulfide

ERK:

Extracellular signal Regulated-Kinase

GSH:

Glutathione

H2S:

Hydrogen Sulfide

HO-1:

Heme Oxygenase-1

IL-1β, -2, -6, 10, -12, -17:

Interleukin-1, -6, -10, -17

IFN-γ:

Interferon γ

JNK:

c-Jun NH2-terminal kinase

Keap1:

Kelch ECH-associated protein 1

MAPK:

Mitogen-Activated Protein Kinase

MEK:

MAPK/ERK kinase

NF-κB:

Nuclear Factor-κB

NK:

Natural Killers

NQO-1:

NAD(P)H quinone dehydrogenase 1

NRF-2:

Nuclear factor erythroid 2-related factor-2

OSCs:

Organic Sulfur Compounds

PI3 K/AKT:

Phosphatidylinositol-3-kinase/AKT

ROS:

Reactive Oxygen Species

SAC:

S-alkyl(en)yl-l-cysteine sulfoxide

SAMC:

S-allylmercaptocysteine

R-SH:

Sulfhydryl

TGF-β:

Transforming Growth Factor-β

TNF-α:

Tumor Necrosis Factor-α

TST:

Thiosulfate Sulfurtransferase (rhodanese)

TRAIL:

(TNF-α)-related apoptosis inducing ligand

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Acknowledgements

EY is a recipient of a Télévie Luxembourg fellowship. This work was supported by the “Recherche Cancer et Sang” Foundation, the “Recherches Scientifiques Luxembourg” Association, the “Een Häerz fir kriibskrank Kanner” Association, the Action LIONS “Vaincre le Cancer” Association, and by Télévie Luxembourg. MD is supported by the NRF, the MEST of Korea for Tumor Microenvironment GCRC 2011-0030001 Grant, and by Brain Korea (BK21) PLUS program.

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  1. Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Hôpital Kirchberg, 9, Rue Edward Steichen, 2540, Luxembourg, Luxembourg

    Esma Yagdi Efe & Mario Dicato

  2. Department of Pharmacy, College of Pharmacy, Seoul National University, Building 29 Room 233, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, South Korea

    Marc Diederich

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  1. Esma Yagdi Efe
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Yagdi Efe, E., Dicato, M. & Diederich, M. Modulation of hydrogen sulfide gasotransmitter limits the proven benefits of garlic. Phytochem Rev 18, 1167–1180 (2019). https://doi.org/10.1007/s11101-019-09634-y

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