Intracellular Diagnostics: Hunting for the Mode of Action of Redox-Modulating Selenium Compounds in Selected Model Systems

Redox-modulating compounds derived from natural sources, such as redox active secondary metabolites, are currently of considerable interest in the field of chemoprevention, drug and phytoprotectant development. Unfortunately, the exact and occasionally even selective activity of such products, and the underlying (bio-)chemical causes thereof, are often only poorly understood. A combination of the nematode- and yeast-based assays provides a powerful platform to investigate a possible biological activity of a new compound and also to explore the “redox link” which may exist between its activity on the one side and its chemistry on the other. Here, we will demonstrate the usefulness of this platform for screening several selenium and tellurium compounds for their activity and action. We will also show how the nematode-based assay can be used to obtain information on compound uptake and distribution inside a multicellular organism, whilst the yeast-based system can be employed to explore possible intracellular mechanisms via chemogenetic screening and intracellular diagnostics. Whilst none of these simple and easy-to-use assays can ultimately substitute for in-depth studies in human cells and animals, these methods nonetheless provide a first glimpse on the possible biological activities of new compounds and offer direction for more complicated future investigations. They may also uncover some rather unpleasant biochemical actions of certain compounds, such as the ability of the trace element supplement selenite to induce DNA strand breaks.

[1]  Tomislav Buric,et al.  Synthesis of amphiphilic, chalcogen-based redox modulators with in vitro cytotoxic activity against cancer cells, macrophages and microbes , 2014 .

[2]  G. Kirsch,et al.  Recent Advances in Redox Active Plant and Microbial Products , 2014, Springer Netherlands.

[3]  M. Montenarh,et al.  Comparison between the effects of diallyl tetrasulfide on human retina pigment epithelial cells (ARPE-19) and HCT116 cells. , 2013, Biochimica et biophysica acta.

[4]  J. Tomblin,et al.  Selenium (sodium selenite) causes cytotoxicity and apoptotic mediated cell death in PLHC-1 fish cell line through DNA and mitochondrial membrane potential damage. , 2013, Ecotoxicology and environmental safety.

[5]  M. Montenarh,et al.  Diallyl tetrasulfane activates both the eIF2α and Nrf2/HO-1 pathways. , 2013, Biochimica et biophysica acta.

[6]  M. Chovanec,et al.  Selenium- and tellurium-containing redox modulators with distinct activity against macrophages: possible implications for the treatment of inflammatory diseases , 2012 .

[7]  P. Griač,et al.  Selenium toxicity toward yeast as assessed by microarray analysis and deletion mutant library screen: a role for DNA repair. , 2012, Chemical research in toxicology.

[8]  D. Dhawan,et al.  Selenium as a modulator of membrane stability parameters and surface changes during the initiation phase of 1,2-dimethylhydrazine induced colorectal carcinogenesis , 2012, Molecular and Cellular Biochemistry.

[9]  Claus Jacob,et al.  Deciphering intracellular targets of organochalcogen based redox catalysts , 2012 .

[10]  C. Nicco,et al.  The organotelluride catalyst LAB027 prevents colon cancer growth in the mice , 2011, Cell Death and Disease.

[11]  K. Becker,et al.  Selective antimicrobial activity associated with sulfur nanoparticles. , 2011, Journal of biomedical nanotechnology.

[12]  C. Jacob,et al.  Selenium- and tellurium-containing multifunctional redox agents as biochemical redox modulators with selective cytotoxicity. , 2010, Chemistry.

[13]  A. Zada,et al.  Synthesis and selective anticancer activity of organochalcogen based redox catalysts. , 2010, Journal of medicinal chemistry.

[14]  M. Yamashita,et al.  Identification of a Novel Selenium-containing Compound, Selenoneine, as the Predominant Chemical Form of Organic Selenium in the Blood of Bluefin Tuna* , 2010, The Journal of Biological Chemistry.

[15]  M. Chovanec,et al.  Investigations on the role of base excision repair and non-homologous end-joining pathways in sodium selenite-induced toxicity and mutagenicity in Saccharomyces cerevisiae. , 2010, Mutagenesis.

[16]  M. Chovanec,et al.  Rad52 has a role in the repair of sodium selenite-induced DNA damage in Saccharomyces cerevisiae. , 2008, Mutation research.

[17]  G. Mugesh,et al.  Selenium Analogues of Antithyroid Drugs – Recent Developments , 2008, Chemistry & biodiversity.

[18]  M. Chovanec,et al.  Toxicity and mutagenicity of selenium compounds in Saccharomyces cerevisiae. , 2008, Mutation research.

[19]  A. A. Razak,et al.  Incorporation of tellurium into amino acids and proteins in a tellurium-tolerant fungi , 1989, Biological Trace Element Research.

[20]  E. Markova,et al.  Relative contribution of homologous recombination and non-homologous end-joining to DNA double-strand break repair after oxidative stress in Saccharomyces cerevisiae. , 2006, DNA repair.

[21]  R. Gaugler,et al.  Assessment ofBacillus thuringiensis serotype 14 andSteinernema feltiae [Nematoda: Steinernematidae] for control of theSimulium vectors of onchocerciasis in Mexico , 1983, Entomophaga.

[22]  Janet E. Holley,et al.  Targeting oxidative stress-related diseases: organochalcogen catalysts as redox sensitizers. , 2003, Biochemical pharmacology.

[23]  S. Fedi,et al.  Reduction of potassium tellurite to elemental tellurium and its effect on the plasma membrane redox components of the facultative phototroph Rhodobacter capsulatus , 2003, Protoplasma.

[24]  C. Jacob,et al.  Redox catalysts as sensitisers towards oxidative stress , 2003, FEBS letters.

[25]  M. de la Torre.  Challenges for mass production of nematodes in submerged culture. , 2003, Biotechnology advances.

[26]  H. Sies,et al.  Chemistry of biologically important synthetic organoselenium compounds. , 2001, Chemical reviews.

[27]  G. Powis,et al.  Water-soluble organotellurium compounds inhibit thioredoxin reductase and the growth of human cancer cells. , 2000, Anti-cancer drug design.

[28]  D. Kirkpatrick,et al.  Selenium and the thioredoxin redox system: effects on cell growth and death. , 1997, Oncology research.

[29]  G. Paine-Murrieta,et al.  Diaryl chalcogenides as selective inhibitors of thioredoxin reductase and potential antitumor agents. , 1997, Anticancer research.

[30]  M. Haberal,et al.  The stabilizing effect of vitamin E, selenium and zinc on leucocyte membrane permeability: a study in vitro. , 1987, Burns, including thermal injury.

[31]  D. W. Gruenwedel.  Differential effects of sodium selenite and methylmercury(II) on membrane permeability and DNA replication in HeLa S3 carcinoma cells: a preliminary report regarding the modification of organomercurial toxicity by selenium compounds. , 1984, Advances in experimental medicine and biology.

[32]  S. G. Ghurye.  On the use of student's t-test in an asymmetrical population. , 1949, Biometrika.