Comparison between the effects of diallyl tetrasulfide on human retina pigment epithelial cells (ARPE-19) and HCT116 cells

Saidu, Nathaniel Edward Bennett; Asali, Imad Abu; Czepukojc, Brigitte; Seitz, Berthold; Jacob, Claus; Montenarh, Mathias

doi:10.1016/j.bbagen.2013.08.004

Cited by 24 publications

(21 citation statements)

References 34 publications

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“…This concept assumes that the cysteine proteins and enzymes in cells are sensors of oxidative stress, and that their sequential and often reversible oxidative modification during an oxidative onslaught triggers widespread cellular signalling which enables the cell to respond adequately, either by mounting an antioxidant defence or by shutting down via apoptosis [5]. In subsequent years, numerous studies have confirmed this idea of a gradual, measured and often complicated and cell type-specific response conveyed by cysteine proteins with different reactivity or sensitivity towards different oxidative modifiers [28,36,37,38,39,40]. …”

Section: The Year 2003: Gestalt Switch In the Field Of Rss Researchmentioning

confidence: 99%

“…Traditional thiol-based antioxidants may also be considered as reducing RSS, although one has to be extraordinarily careful here. Many of these antioxidants, such as diallyltrisulfide (DATS) or diallyltetrasulfide (DATTS), do not act as reducing agents at all, but oxidize certain cysteine proteins, such as Keap-1, thereby triggering cellular signalling cascades which eventually lead to an—indirect—antioxidant response [39,40]. …”

Section: What Are Rss?mentioning

confidence: 99%

“…The link between RSS and increased levels of oxidative stress is far from surprising, as RSS often consume reduced thiols and hence directly or indirectly lead to an increase of ROS concentrations. This kind of selective oxidation can be exploited in the therapy against microbes and is also under consideration in the context of cancer therapy [39,40,107,108,115]. Recent studies involving a wide spectrum of 1,2-dithiole-3-thiones have associated some of these sulfur compounds with the induction of cytoprotective Phase 2 enzymes, but also with the inhibition of histone deacetylase enzymes [116,117].…”

Section: Food For Thoughtmentioning

confidence: 99%

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The Reactive Sulfur Species Concept: 15 Years On

et al. 2017

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Fifteen years ago, in 2001, the concept of “Reactive Sulfur Species” or RSS was advocated as a working hypothesis. Since then various organic as well as inorganic RSS have attracted considerable interest and stimulated many new and often unexpected avenues in research and product development. During this time, it has become apparent that molecules with sulfur-containing functional groups are not just the passive “victims” of oxidative stress or simple conveyors of signals in cells, but can also be stressors in their own right, with pivotal roles in cellular function and homeostasis. Many “exotic” sulfur-based compounds, often of natural origin, have entered the fray in the context of nutrition, ageing, chemoprevention and therapy. In parallel, the field of inorganic RSS has come to the forefront of research, with short-lived yet metabolically important intermediates, such as various sulfur-nitrogen species and polysulfides (Sx2−), playing important roles. Between 2003 and 2005 several breath-taking discoveries emerged characterising unusual sulfur redox states in biology, and since then the truly unique role of sulfur-dependent redox systems has become apparent. Following these discoveries, over the last decade a “hunt” and, more recently, mining for such modifications has begun—and still continues—often in conjunction with new, innovative and complex labelling and analytical methods to capture the (entire) sulfur “redoxome”. A key distinction for RSS is that, unlike oxygen or nitrogen, sulfur not only forms a plethora of specific reactive species, but sulfur also targets itself, as sulfur containing molecules, i.e., peptides, proteins and enzymes, preferentially react with RSS. Not surprisingly, today this sulfur-centred redox signalling and control inside the living cell is a burning issue, which has moved on from the predominantly thiol/disulfide biochemistry of the past to a complex labyrinth of interacting signalling and control pathways which involve various sulfur oxidation states, sulfur species and reactions. RSS are omnipresent and, in some instances, are even considered as the true bearers of redox control, perhaps being more important than the Reactive Oxygen Species (ROS) or Reactive Nitrogen Species (RNS) which for decades have dominated the redox field. In other(s) words, in 2017, sulfur redox is “on the rise”, and the idea of RSS resonates throughout the Life Sciences. Still, the RSS story isn’t over yet. Many RSS are at the heart of “mistaken identities” which urgently require clarification and may even provide the foundations for further scientific revolutions in the years to come. In light of these developments, it is therefore the perfect time to revisit the original hypotheses, to select highlights in the field and to question and eventually update our concept of “Reactive Sulfur Species”.

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Section: The Year 2003: Gestalt Switch In the Field Of Rss Researchmentioning

confidence: 99%

Section: What Are Rss?mentioning

confidence: 99%

Section: Food For Thoughtmentioning

confidence: 99%

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The Reactive Sulfur Species Concept: 15 Years On

et al. 2017

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“…A reduction in cell number can be due to the induction of apoptosis, a process studied extensively for many natural organic sulfur compounds (6,13,16,18). To investigate this possibility, we treated HCT116 cells with 50 µm ATTSB or 50 µM ATSEE.…”

Section: Resultsmentioning

confidence: 99%

“…Interestingly, it has also been shown by a number of independent studies that cancer cells are much more sensitive to the treatment with diallyl mono-and polysulfides when compared to normal cells. Here, cancer cells usually die by apoptosis whereas normal healthy cells survive (13)(14)(15)(16). Whilst such selectivity for cancer cells is highly unusual for molecules derived from non-toxic, even edible plants, it can be explained in part by the particular predisposition of cancer cells to react highly sensitively to externally induced changes in their intracellular redox state (10,17).…”

Section: Introductionmentioning

confidence: 99%

A scent of therapy: Synthetic polysulfanes with improved physico-chemical properties induce apoptosis in human cancer cells

Allah

Schwind

Asali

et al. 2015

International Journal of Oncology

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Diallyl sulfanes derived from edible plants are highly potent compounds which at sub-millimolar concentrations are able to induce the formation of reactive oxygen species (ROS) in a variety of different cells, where they often cause an altered redox status. The loss of cellular thiols and/or formation of ROS subsequently triggers a range of cellular responses, including the induction of apoptosis. A great disadvantage of natural diallyl mono- and polysulfanes, however, is their inherent insolubility in water and the extremely bad odour which limits their practical use in humans. Here, we present the synthesis and biological evaluation of two new, especially designed polysulfanes, namely the trisulfide 1-Allyl-3-(2-ethoxyethyl)trisulfide (ATSEE) and the tetrasulfide Allyl-4-benzyltetrasulfide (ATTSB), which are nearly odourless. Both compounds produce O2•- radicals in HCT116 cells and both induce an oxidative defence signalling. Cell viability is especially reduced by the tetrasulfane ATTSB, with an arrest of the cell cycle in the G2-phase. In contrast, the trisulfane ATSEE does not inhibit the cell cycle. In agreement with these findings, treatment of HCT116 cells with ATTSB ultimately results in apoptosis whereas only limited induction of apoptosis has been detected for cells treated with ATSEE. We further show that antioxidative defence mechanisms and death response signalling run in parallel and the dominant pathway decides the fate of the cell. Thus, our results not only illuminate the intricate mode of action of certain polysulfanes; they also demonstrate that the new odourless tri- and tetrasulfanes exhibit a similar activity compared to their natural counterparts, yet are easier to handle and also deprived of the offensive odour which so far has prevented most practical applications of such polysulfanes, at least in the context of medicine.

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The garlic compound ajoene targets protein folding in the endoplasmic reticulum of cancer cells

Kaschula

Hunter

Cotton

et al. 2015

Molecular Carcinogenesis

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Ajoene is a natural allylsulfur compound found in crushed garlic that arrests growth and induces apoptosis in cancer cells. To gain mechanistic insights into the cytotoxicity of ajoene in cancer cells, two fluorescently labelled ajoene analogs with dansyl- (DP) and fluorescein- (FOX) tags were synthesized. The tagged ajoenes were found to retain their activity at inhibiting proliferation and inducing apoptosis in MDA-MB-231 human breast-cancer and WHCO1 human esophageal-cancer cells. Both tagged ajoenes localized to the endoplasmic reticulum (ER) in MDA-MB-231 cells as observed by live cell confocal laser scanning microscopy (CLSM) and confirmed by generating an MDA-MB-231 cell line expressing yellow fluorescent protein (YFP) in the ER. DP appears to S-thiolate multiple protein targets in MDA-MB-231 cells as observed by immunoblotting under non-reducing conditions only; and a competition assay demonstrated that DP and Z-ajoene in fact share the same target. Ajoene S-thiolation interfered with protein folding and led to an accumulation of misfolded protein aggregates and activated the unfolded protein response (UPR). Consistent with this mechanism, increased levels of GRP78 and total ubiquitinated proteins were observed; and an ER-folded protein, type-1 collagen, was tracked to the proteasome following ajoene treatment. The intracellular protein aggregates were observed by CLSM and transmission electron microscopy (TEM). This is the first time that ajoene has been shown to target protein folding in the ER of cancer cells. © 2015 Wiley Periodicals, Inc.

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Comparison between the effects of diallyl tetrasulfide on human retina pigment epithelial cells (ARPE-19) and HCT116 cells

Cited by 24 publications

References 34 publications

The Reactive Sulfur Species Concept: 15 Years On

The Reactive Sulfur Species Concept: 15 Years On

A scent of therapy: Synthetic polysulfanes with improved physico-chemical properties induce apoptosis in human cancer cells

The garlic compound ajoene targets protein folding in the endoplasmic reticulum of cancer cells

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