title: H2S-releasing nanoemulsions: a new formulation to inhibit tumor cells proliferation and improve tissue repair.
abstract: The improvement of solubility and/or dissolution rate of poorly soluble natural compounds is an ideal strategy to make them optimal candidates as new potential drugs. Accordingly, the allyl sulfur compounds and omega-3 fatty acids are natural hydrophobic compounds that exhibit two important combined properties: cardiovascular protection and antitumor activity. Here, we have synthesized and characterized a novel formulation of diallyl disulfide (DADS) and α-linolenic acid (ALA) as protein-nanoemulsions (BAD-NEs), using ultrasounds. BAD-NEs are stable over time at room temperature and show antioxidant and radical scavenging property. These NEs are also optimal H2S slow-release donors and show a significant anti-proliferative effect on different human cancer cell lines: MCF-7 breast cancer and HuT 78 T-cell lymphoma cells. BAD-NEs are able to regulate the ERK1/2 pathway, inducing apoptosis and cell cycle arrest at the G0/G1 phase. We have also investigated their effect on cell proliferation of human adult stem/progenitor cells. Interestingly, BAD-NEs are able to improve the Lin- Sca1+ human cardiac progenitor cells (hCPC) proliferation. This stem cell growth stimulation is combined with the expression and activation of proteins involved in tissue-repair, such as P-AKT, α-sma and connexin 43. Altogether, our results suggest that these antioxidant nanoemulsions might have potential application in selective cancer therapy and for promoting the muscle tissue repair.
authors.affiliation: Department of Chemical Sciences and Technologies, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Ciocci
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Egidio
authors.initials: E
authors.lastname: Iorio
authors.affiliation: Department of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Felicia
authors.initials: F
authors.lastname: Carotenuto
authors.affiliation: Department of Chemical Sciences and Technologies, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Haneen A
authors.initials: HA
authors.lastname: Khashoggi
authors.affiliation: Department of Industrial Engineering, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Nanni
authors.affiliation: Department of Chemical Sciences and Technologies, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Melino
mesh_terms: D000498:Allyl Compounds / Q000378:metabolism / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002316:Cardiotonic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004220:Disulfides / Q000378:metabolism / Q000494:pharmacology*; D004655:Emulsions / Q000737:chemistry; D005260:Female; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D061986:MCF-7 Cells; D008855:Microscopy, Electron, Scanning; D009206:Myocardium / Q000166:cytology; D049329:Nanostructures / Q000737:chemistry / Q000648:ultrastructure; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D013234:Stem Cells / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000498:Allyl Compounds; D000970:Antineoplastic Agents; D002316:Cardiotonic Agents; D004220:Disulfides; D004655:Emulsions; C028009:diallyl disulfide; D006862:Hydrogen Sulfide
keywords: antioxidants; cancer; garlic; hydrogen sulfide; omega-3 fatty acid