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.
Highlights
Epidemiological and preclinical studies support the effect of garlic (Allium sativum L.) as a cardiovascular-protective agent with chemopreventive and anticarcinogenic effects
Among Organo-Sulfur Compounds (OSCs) derived from garlic, diallyl-disulfide (DADS) seems to be the most effective at reducing the growth of human tumor cells derived from skin, colon and lung [12,26]
Scan Electro Microscopy (SEM) analysis of BADNE confirms the presence of spheres with a diameter less than 1 μm (Figure 2) SEM sample preparation by drying and under vacuum metallization lead to an increase in size of the spheres
Summary
Epidemiological and preclinical studies support the effect of garlic (Allium sativum L.) as a cardiovascular-protective agent with chemopreventive and anticarcinogenic effects. Allyl sulfur compounds show anti-proliferative effects on cancer cells by blocking the G1/S or G2/M cell cycle phases [11, 20, 21,22,23,24]. Among OSCs derived from garlic, diallyl-disulfide (DADS) seems to be the most effective at reducing the growth of human tumor cells derived from skin, colon and lung [12,26]. Omega-3 fatty acids as well as garlic OSCs are www.impactjournals.com/oncotarget natural compounds that exhibit two combined properties: cardiovascular protection [35, 36] and antitumor activity [37, 38]. Other studies confirm ALA as a potential dietary agent of chemoprevention on human breast cancer cells. Its anti-carcinogenic property seems related to its ability to affect the growth of breast and colon cancers [36,37,38, 41] as well as to affect cell death, with cytochrome c translocation, caspase-3 activation, and PARP degradation [42]
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