Garlic has long been considered as a natural remedy against a range of human illnesses, including various bacterial, viral and fungal infections. This kind of antibiotic activity of garlic has mostly been associated with the thiosulfinate allicin. Even so, recent studies have pointed towards a significant biological activity of trisulfides and tetrasulfides found in various Allium species, including a wide range of antibiotic properties and the ability of polysulfides to cause the death of certain cancer cells. The chemistry underlying the biological activity of these polysulfides is currently emerging. It seems to include a combination of several distinct transformations, such as oxidation reactions, superoxide radical and peroxide generation, decomposition with release of highly electrophilic S(x) species, inhibition of metalloenzymes, disturbance of metal homeostasis and membrane integrity and interference with different cellular signalling pathways. Further research in this area is required to provide a better understanding of polysulfide reactions within a biochemical context. This knowledge may ultimately form the basis for the development of 'green' antibiotics, fungicides and possibly anticancer agents with dramatically reduced side effects in humans.

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Naturally occurring organic sulfur compounds (OSCs), such as linear allylsulfides from Allium species, are attracting attention in cancer research, since several OSCs were shown to act beneficially both in chemoprevention and in chemotherapy, while hardly exerting any harmful side effects. Hence, we investigated the possible role of different OSCs in the treatment of leukemia. Thereby, we found that the compounds tested in this study induced apoptosis in U937 cells, with an efficiency depending on the number of sulfides, and selected the most promising candidate, diallyltetrasulfide (Al2S4), for detailed mechanistic studies. Here we show that Al2S4 induced an accumulation of cells in early mitosis (G2/M phase), followed by the activation of caspase-dependent apoptosis. The compound counteracted different anti-apoptotic Bcl-2 family members (Bcl-xL, phospho-Bad and Bcl-2), promoted activation of Bax and Bak and induced the release of cytochrome c into the cytoplasm. Treatment by Al2S4 let to the identification of early apoptotic events including Bcl-xL degradation, Bak activation and release of cytochrome c followed by late events including Bcl-2 proteolysis, Bax activation, Bad dephosphorylation, caspase activation, nuclear fragmentation and phosphatidylserine exposure.

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Sulphur metabolism in plants provides a wealth of natural products, including several chemically unusual substances, such as thiosulphinates, polysulphides and isothiocyanates. Many of these reactive sulphur species (RSS) exhibit a distinct redox behaviour in vitro, which translates into a rather interesting biological activity in vivo, such as antibiotic, fungicidal, pesticidal or anticancer activity. While the molecular basis for such activity has long remained obscure, research into sulphur-based redox systems during the past 5-10 years has achieved a better knowledge of the in vitro properties of RSS and has led to an improved understanding of their impact on intracellular redox signalling and control pathways in living cells. It has become apparent that the redox chameleon sulphur occurs in biological systems in about 10 different oxidation states, which give rise to an extensive and complicated network of sulphur-based redox events. Together, natural sulphur products from plants and their intracellular targets provide the basis for innovative design of novel antibiotics, fungicides, pesticides and anticancer agents.

Our findings showed that pharmacological activation of Epac-Rap1 improves cardiac function through better survival, adhesion and differentiation of transplanted cells. Transplantation of these MSCs in the infarct area restored functional myocardium.