H2S-releasing nanoemulsions: a new formulation to inhibit tumor cells proliferation and improve tissue repair

Oncotarget. 2016 Dec 20;7(51):84338-84358. doi: 10.18632/oncotarget.12609.

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.

Keywords: antioxidants; cancer; garlic; hydrogen sulfide; omega-3 fatty acid.

MeSH terms

  • Allyl Compounds / metabolism
  • Allyl Compounds / pharmacology*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Cardiotonic Agents / chemistry
  • Cardiotonic Agents / metabolism
  • Cardiotonic Agents / pharmacology
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Disulfides / metabolism
  • Disulfides / pharmacology*
  • Emulsions / chemistry
  • Female
  • Humans
  • Hydrogen Sulfide / metabolism*
  • MCF-7 Cells
  • Microscopy, Electron, Scanning
  • Myocardium / cytology
  • Nanostructures / chemistry
  • Nanostructures / ultrastructure
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Stem Cells / drug effects*
  • Stem Cells / metabolism

Substances

  • Allyl Compounds
  • Antineoplastic Agents
  • Cardiotonic Agents
  • Disulfides
  • Emulsions
  • diallyl disulfide
  • Hydrogen Sulfide