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Modulation of hydrogen sulfide gasotransmitter limits the proven benefits of garlic

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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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3-Mercaptopyruvate Sulfurtransferase


Aged garlic extracts


Allyl Mercaptan


Allyl Methyl sulfide


Allyl Methyl Sulfoxide


Allyl Methyl Sulfone


Aminooxyacetic Acid


Bcl-2-associated X protein


B-cell lymphoma 2


BH3 interacting domain death agonist


Cysteine Aminotransferase








Diallyl Disulfide


Diallyl Sulfide


Diallyl Trisulfide


Diallyl Tetrasulfide


Dibenzyl Tetrasulfide


Extracellular signal Regulated-Kinase




Hydrogen Sulfide


Heme Oxygenase-1

IL-1β, -2, -6, 10, -12, -17:

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


Interferon γ


c-Jun NH2-terminal kinase


Kelch ECH-associated protein 1


Mitogen-Activated Protein Kinase


MAPK/ERK kinase


Nuclear Factor-κB


Natural Killers


NAD(P)H quinone dehydrogenase 1


Nuclear factor erythroid 2-related factor-2


Organic Sulfur Compounds




Reactive Oxygen Species


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






Transforming Growth Factor-β


Tumor Necrosis Factor-α


Thiosulfate Sulfurtransferase (rhodanese)


(TNF-α)-related apoptosis inducing ligand


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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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Yagdi Efe, E., Dicato, M. & Diederich, M. Modulation of hydrogen sulfide gasotransmitter limits the proven benefits of garlic. Phytochem Rev 18, 1167–1180 (2019).

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