Abstract
Melanoma is the most common form of skin cancer. Given its high mortality, the interest in the search of preventive measures, such as dietary factors, is growing significantly. In this study we tested, in vitro and in vivo, the potential anti-cancer effect of the acetyl deacylasadisulfide (ADA), a vinyl disulfide compound, isolated and purified from asafoetida a foul-smelling oleo gum-resin of dietary and medicinal relevance. ADA markedly suppressed proliferation of human melanoma cell lines by inducing apoptosis. Moreover, treatment of melanoma cells with ADA reduced nuclear translocation and activation of NF-κB, decreased the expression of the anti-apoptotic proteins c-FLIP, XIAP, and Bcl-2 and inhibited the phosphorylation and activation of both AKT and ERK proteins, two of the most frequently deregulated pathways in melanoma. Finally, the results obtained in vitro were substantiated by the findings that ADA significantly and dose-dependently reduced lung metastatic foci formation in C57BL/6 mice. In conclusion, our findings suggest that ADA significantly inhibits melanoma progression in vivo and could represent an important lead compound for the development of new anti-metastatic agents.
Highlights
Hydrogen sulfide (H2S) is a gaseous signaling molecule that plays important roles in a variety of biological functions, in health and disease (Szabo, 2007; Kimura, 2011; Whiteman et al, 2011; Wang, 2012)
We found that all the sulfur-containing compounds acetyl deacylasadisulfide (ADA), Propionyl deacylasadisulfide (PDA), foetisulfide A (FSA), arachyl deacylasadisulfide (ARDA), and DA inhibited the proliferation of melanoma cells with different potency (Figure 1)
We describe for the first time, the anti-cancer properties of ADA, a naturally occurring hydrogen sulfide (H2S) donor, isolated and purified from Ferula assa-foetida L
Summary
Hydrogen sulfide (H2S) is a gaseous signaling molecule that plays important roles in a variety of biological functions, in health and disease (Szabo, 2007; Kimura, 2011; Whiteman et al, 2011; Wang, 2012). The physiological production of H2S is mainly deputed to the activity of three enzymes: Cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST). Endogenous generated H2S has been involved in the regulation of cancer biological processes and, according to the cancer type, different roles can be ascribed to the molecule as recently reviewed (Szabo, 2016). H2S generated by over-expressed CSE appears to be involved in the progression of the disease (Panza et al, 2015). While inhibition of H2S biosynthesis produces anticancer effects, many reports show that H2S donors, of either natural or chemical origin, exert anticancer actions in vitro and in vivo
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