Abstract
Natural organosulfur compounds (OSCs) from Allium sativum L. display antioxidant and chemo-sensitization properties, including the in vitro inhibition of tumor cell proliferation through the induction of apoptosis. Garlic water- and oil-soluble allyl sulfur compounds show distinct properties and the capability to inhibit the proliferation of tumor cells. In the present study, we optimized a new protocol for the extraction of water-soluble compounds from garlic at low temperatures and the production of glutathionyl-OSC conjugates during the extraction. Spontaneously, Cys/GSH-mixed-disulfide conjugates are produced by in vivo metabolism of OSCs and represent active molecules able to affect cellular metabolism. Water-soluble extracts, with (GSGaWS) or without (GaWS) glutathione conjugates, were here produced and tested for their ability to release hydrogen sulfide (H2S), also in the presence of reductants and of thiosulfate:cyanide sulfurtransferase (TST) enzyme. Thus, the TST catalysis of the H2S-release from garlic OSCs and their conjugates has been investigated by molecular in vitro experiments. The antiproliferative properties of these extracts on the human T-cell lymphoma cell line, HuT 78, were observed and related to histone hyperacetylation and downregulation of GAPDH expression. Altogether, the results presented here pave the way for the production of a GSGaWS as new, slowly-releasing hydrogen sulfide extract for potential therapeutic applications.
Highlights
The health benefits of Allium species are widely attributed to enzyme transformed organosulfur compounds (OSCs), named thiosulfinates, which are the dominating organosulfur species in fresh garlic and onion tissue macerates, representing between 50% and 94% of the organo-compounds [1].These compounds exhibit intriguing biological properties: antimicrobial, antioxidant [2,3] and anti-inflammatory actions [4] that are able to upregulate detoxification/cytoprotective enzymes [5,6], such as quinine reductase [1,7] and GST [8,9]
The RP-HPLC analysis of extracts performed at low temperatures showed a better resolution of the elution peaks, very likely due to a minor OSC oxidation in the extraction phase, which is consistent with the presence of a few oxidized forms with limited hydrophobic differences
Considering the ability of the garlic WS extracts to interact with the catalytic cysteine of the thiosulfate:cyanide sulfurtransferase (TST), we investigated the effect on the expression of glyceraldehyde 3-phosphate dehydrogenase (GAPDH), a key glycolytic enzyme characterized by the presence of a cysteine in the active site
Summary
The health benefits of Allium species are widely attributed to enzyme transformed organosulfur compounds (OSCs), named thiosulfinates, which are the dominating organosulfur species in fresh garlic and onion tissue macerates, representing between 50% and 94% of the organo-compounds [1] These compounds exhibit intriguing biological properties: antimicrobial, antioxidant [2,3] and anti-inflammatory actions [4] that are able to upregulate detoxification/cytoprotective enzymes [5,6], such as quinine reductase [1,7] and GST [8,9]. The biochemical transformations of these compounds within the cell and the resulting adducts with the thiol functional groups of the proteins could constitute a relevant event to uncover their anticancer properties They can freely permeate cell membranes and rapidly react with Cys or GSH to form intracellular Cys/GSH mixed-disulfide conjugates. Cys/GSH-mixed-disulfide conjugates are among the derivates that can be formed from Allium sativum L. tissue constituents and in vivo metabolism
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