title: Glutathione-garlic sulfur conjugates: slow hydrogen sulfide releasing agents for therapeutic applications.
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.
authors.affiliation: Department of Chemical Sciences and Technologies, University of Rome Tor Vergata, via della Ricerca Scientifica, Rome 00133, Italy. ashif.biochim@gmail.com.
authors.forename: Ashif Iqbal
authors.initials: AI
authors.lastname: Bhuiyan
authors.affiliation: Department of Professional Chemistries and Pharmacognosy, University of Medicine, Tirana, Str. "Dibra", Nr. 371, Tirana 1000, Albania. toskavilma@gmail.com.
authors.forename: Vilma Toska
authors.initials: VT
authors.lastname: Papajani
authors.affiliation: Department of Chemical Sciences and Technologies, University of Rome Tor Vergata, via della Ricerca Scientifica, Rome 00133, Italy. paci@uniroma2.it.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Paci
authors.affiliation: Department of Chemical Sciences and Technologies, University of Rome Tor Vergata, via della Ricerca Scientifica, Rome 00133, Italy. melinos@uniroma2.it.
authors.forename: Sonia
authors.initials: S
authors.lastname: Melino
mesh_terms: D055162:Biocatalysis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D056148:Chromatography, Reverse-Phase; D003080:Cold Temperature; D005737:Garlic / Q000737:chemistry*; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D016399:Lymphoma, T-Cell / Q000473:pathology; D008856:Microscopy, Fluorescence; D008970:Molecular Weight; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D019163:Reducing Agents / Q000494:pharmacology; D012995:Solubility; D013455:Sulfur / Q000378:metabolism*; D013457:Sulfur Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D013879:Thioredoxins / Q000378:metabolism; D013884:Thiosulfate Sulfurtransferase / Q000037:antagonists & inhibitors / Q000378:metabolism; D014867:Water / Q000737:chemistry
chemical_list: D010936:Plant Extracts; D019163:Reducing Agents; D013457:Sulfur Compounds; D014867:Water; D013879:Thioredoxins; D013455:Sulfur; D013884:Thiosulfate Sulfurtransferase; D005978:Glutathione; D006862:Hydrogen Sulfide