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The natural product allicin is a reactive sulfur species (RSS) from garlic (Allium sativumL.). Neuroblastoma (NB) is an early childhood cancer arising from the developing peripheral nervous system. Ornithine decarboxylase (ODC) is a rate-limiting enzyme in the biosynthesis of polyamines, which are oncometabolites that contribute to cell proliferation in NB and other c-MYC/MYCN-driven cancers. Both c-MYC and MYCN directly transactivate the E-box gene ODC1, a validated anticancer drug target. We identified allicin as a potent ODC inhibitor in a specific radioactive in vitroassay using purified human ODC. Allicin was ∼23 000-fold more potent (IC50= 11 nM) than DFMO (IC50= 252 μM), under identical in vitroassay conditions. ODC is a homodimer with 12 cysteines per monomer, and allicin reversibly S-thioallylates cysteines. In actively proliferating human NB cells allicin inhibited ODC enzyme activity, reduced cellular polyamine levels, inhibited cell proliferation (IC509–19 μM), and induced apoptosis. The natural product allicin is a new ODC inhibitor and could be developed for use in conjunction with other anticancer treatments, the latter perhaps at a lower than usual dosage, to achieve drug synergism with good prognosis and reduced adverse effects.

Background: As a chalcogen selenium has an interesting role in biology e.g. when it replaces sulfur in the amino acid cysteine, giving selenocysteine, which has an essential role in mammalian redox metabolism, being an essential part of the active site of mammalian glutathione peroxidase enzymes. Like other chalcogens selenium has several formal oxidation states and selenium compounds can interact with the cell's redox system, which must be tightly regulated for cell survival. Thus, selenium compounds can be physiologically active in cells and have potential as tools to investigate cell biochemistry and physiology and, depending on their mode of action, as therapeutic substances in medicine. Methods and Results: This article aims to show the potential that baker's yeast (Saccharomyces cerevisiae), a single-celled organism, offers as a model system for mode-of-action studies for novel and already known selenium compounds of potential therapeutic and biotechnological interest. For this purpose, sodium selenite (Na2SeO3) as an example test compound has been used in a selection of screening procedures to identify genes potentially involved in cellular responses. For example, the glutathione reductase gene seems to be important to protect cells against Na2SeO3. Conclusions: The article is aimed at chemists and hopes to introduce and demystify the biology behind the common tests used with yeast. It is not intended to be an exhaustive treatment of yeast biology and much is missing, which would be found in a comprehensive practical manual, but it is hoped that it will be an introduction for scientists reading outside their specialization and helps making them aware of useful techniques for their own research.

Plants respond to pathogen attack by deploying several defense reactions. Some rely on the activation of preformed components, whereas others depend on changes in transcriptional activity. Using cDNA arrays comprising 13,000 unique expressed sequence tags, changes in the transcriptome ofArabidopsis thalianawere monitored after attempted infection with the bacterial plant pathogen Pseudomonas syringaepv. tomatocarrying the avirulence geneavrRpt2. Sampling at four time points during the first 24 h after infiltration revealed significant changes in the steady state transcript levels of ∼650 genes within 10 min and a massive shift in gene expression patterns by 7 h involving ∼2,000 genes representing many cellular processes. This shift from housekeeping to defense metabolism results from changes in regulatory and signaling circuits and from an increased demand for energy and biosynthetic capacity in plants fighting off a pathogenic attack. Concentrating our detailed analysis on the genes encoding enzymes in glycolysis, the Krebs cycle, the pentose phosphate pathway, the biosynthesis of aromatic amino acids, phenylpropanoids, and ethylene, we observed interesting differential regulation patterns. Furthermore, our data showed potentially important changes in areas of metabolism, such as the glyoxylate metabolism, hitherto not suspected to be components of plant defense.

A procedure which avoids the use of phenol-chloroform and RNAase for the isolation of total DNA fromA. tumefaciens isdescribed. Specific precipitation of protein by 2.5 M ammonium acetate is employed and much of the RNA is removed by an isopropanol precipition step. The procedure yields easily restrictable, good quality DNA and is probably applicable to other Gramnegative bacteria.

The multiplicity of chemical structures of sulfur containing compounds, influenced in part by the element's several oxidation states, directly results in diverse modes of action for sulfur-containing natural products synthesized as secondary metabolites in plants. Sulfur-containing natural products constitute a formidable wall of defence against a wide range of pathogens and pests. Steady progress in the development of new technologies have advanced research in this area, helping to uncover the role of such important plant defence molecules like endogenously-released elemental sulphur, but also deepening current understanding of other better-studied compounds like the glucosinolates. As studies continue in this area, it is becoming increasingly evident that sulfur and sulfur compounds play far more important roles in plant defence than perhaps previously suspected.