Glucose Transporters as a Target for Anticancer Therapy

Tumor growth causes cancer cells to become hypoxic. A hypoxic condition is a hallmark of cancer. Metabolism of cancer cells differs from metabolism of normal cells. Cancer cells prefer the process of glycolysis as a source of ATP. Process of glycolysis generates only two molecules of ATP per one molecule of glucose, whereas the complete oxidative breakdown of one molecule of glucose yields 36 molecules of ATP. Therefore, cancer cells need more molecules of glucose in comparison with normal cells. Increased uptake of glucose by these cells is due to overexpression of glucose transporters, especially GLUT1 and GLUT3, that are hypoxia responsive, as well as other glucose transport proteins. Increased expression of these carrier proteins may be used in anticancer therapy. This phenomenon is used in diagnostic techniques such as FDG-PET. It is also suggested, and there are observations, that therapeutic inhibition of glucose transporters may be a method in treatment of cancer patients. On the other hand, there are described cases, in which upregulation of glucose transporters, as, for example, NIS, which is used in radioiodine therapy, can help patients with cancer. The aim of this review is the presentation of possibilities, and how glucose transporters can be used in anticancer therapy.

5,5-Dialkylluciferins are thermal stable substrates for bioluminescence-based detection systems

Firefly luciferase-based ATP detection assays are frequently used as a sensitive, cost-efficient method for monitoring hygiene in many industrial settings. Solutions of detection reagent, containing a mixture of a substrate and luciferase enzyme that produces photons in the presence of ATP, are relatively unstable and maintain only a limited shelf life even under refrigerated conditions. It is therefore common for the individual performing a hygiene test to manually prepare fresh reagent at the time of monitoring. To simplify sample processing, a liquid detection reagent with improved thermal stability is needed. The engineered firefly luciferase, Ultra-Glo™, fulfills one aspect of this need and has been valuable for hygiene monitoring because of its high resistance to chemical and thermal inactivation. However, solutions containing both Ultra-Glo™ luciferase and its substrate luciferin gradually lose the ability to effectively detect ATP over time. We demonstrate here that dehydroluciferin, a prevalent oxidative breakdown product of luciferin, is a potent inhibitor of Ultra-Glo™ luciferase and that its formation in the detection reagent is responsible for the decreased ability to detect ATP. We subsequently found that dialkylation at the 5-position of luciferin (e.g., 5,5-dimethylluciferin) prevents degradation to dehydroluciferin and improves substrate thermostability in solution. However, since 5,5-dialkylluciferins are poorly utilized by Ultra-Glo™ luciferase as substrates, we used structural optimization of the luciferin dialkyl modification and protein engineering of Ultra-Glo™ to develop a luciferase/luciferin pair that shows improved total reagent stability in solution at ambient temperature. The results of our studies outline a novel luciferase/luciferin system that could serve as foundations for the next generation of bioluminescence ATP detection assays with desirable reagent stability.

Effect of Processing and Radiation Exposure on the Structure and Properties of Polypropylene

While producing polymers as well as during their processing, a certain amount of stabilizers is introduced into the product, which should ensure polymer properties saving during processing and those of polymer products during storage and operation. However, in cases where medical products based on polypropylene are subjected to radiation sterilization, there are not enough stabilizers in it to save their characteristics during operation. In this regard, we made an assessment of the influence of processing conditions on the properties of polypropylene with a different set of stabilizers in the manufacture of products based on it, in order to assess the degree of influence of each technological operation, including the effects of ionizing radiation during sterilization. Processing and radiation exposure are shown to affect the properties of polypropylene. Nevertheless, the effect of ionizing radiation with an absorbed dose of 40-60 kGy exceeds the negative effect of thermo-oxidative breakdown greatly during the extrusion of PP. Polypropylene containing organophosphorus stabilizers (brand PP 1562R) is more susceptible to breakdown. This is indicated by low values of oxidation induction time, breakdown initial temperature, as well as high values of MFI after exposure to electron radiation. PP brand PP H350FF/1 whose stabilizing complex contains phenol-phosphite antioxidants is more resistant to breakdown during processing and sterilization. For both brands under study, it is apparently necessary to increase the content of stabilizing additives in order to save the properties at the level of the original unexposed material.

Energy Conservation via Thioesters in a Non-Enzymatic Metabolism-like Reaction Network

<p><b>Life’s catabolic processes capture chemical energy from the oxidative breakdown of metabolites. In the catabolic pathways at the core of biochemistry, the oxidation of </b>α-<b>ketoacids or aldehydes is coupled to the synthesis of thioesters, whose energy-releasing hydrolysis is in turn coupled to the production of adenosine 5’-triphosphate (ATP). How these processes became linked before life emerged, and thus how the framework for modern bioenergetics was established, is a major problem for understanding the origins of biochemistry. The structure of biochemical networks suggests that the intermediary role of thioesters in biological energy flows, and their central role in biosynthesis, is a consequence of their entry into metabolism at the earliest stage of biochemical evolution. However, how thioesters could have become embedded within a metabolic network before the advent of enzymes remains unclear. Here we demonstrate non-enzymatic oxidant- or light-driven thioester synthesis from biological </b>α-<b>ketoacids and show it can be integrated within an iron-promoted metabolism-like reaction network. The thioesters obtained are those predicted to be pivotal in computational reconstructions of primitive biochemical networks (acetyl, malonyl, malyl and succinyl thioesters), demonstrating a rare convergence between top-down and bottom-up approaches to the origins of metabolism. The diversity and simplicity of conditions that form thioesters from core metabolites suggests the energetic link between thioester synthesis and catabolism was in place at the earliest stage of prebiotic chemistry, constraining the path for the later evolution of life’s phosphorus-based energy currencies.</b></p>

Energy Conservation via Thioesters in a Non-Enzymatic Metabolism-like Reaction Network

<p><b>Life’s catabolic processes capture chemical energy from the oxidative breakdown of metabolites. In the catabolic pathways at the core of biochemistry, the oxidation of </b>α-<b>ketoacids or aldehydes is coupled to the synthesis of thioesters, whose energy-releasing hydrolysis is in turn coupled to the production of adenosine 5’-triphosphate (ATP). How these processes became linked before life emerged, and thus how the framework for modern bioenergetics was established, is a major problem for understanding the origins of biochemistry. The structure of biochemical networks suggests that the intermediary role of thioesters in biological energy flows, and their central role in biosynthesis, is a consequence of their entry into metabolism at the earliest stage of biochemical evolution. However, how thioesters could have become embedded within a metabolic network before the advent of enzymes remains unclear. Here we demonstrate non-enzymatic oxidant- or light-driven thioester synthesis from biological </b>α-<b>ketoacids and show it can be integrated within an iron-promoted metabolism-like reaction network. The thioesters obtained are those predicted to be pivotal in computational reconstructions of primitive biochemical networks (acetyl, malonyl, malyl and succinyl thioesters), demonstrating a rare convergence between top-down and bottom-up approaches to the origins of metabolism. The diversity and simplicity of conditions that form thioesters from core metabolites suggests the energetic link between thioester synthesis and catabolism was in place at the earliest stage of prebiotic chemistry, constraining the path for the later evolution of life’s phosphorus-based energy currencies.</b></p>

Two New Steroidal Saponins from Solanum procumbens

Two new steroidal saponins, solaprocumosides A (1) and B (2), and a known compound paniculonin B (3) were isolated from the aerial parts of Solanum procumbens. Their chemical structures were determined by analysis of HR-ESI-MS and NMR spectra. Compound 1 had ketone functional groups at C-16 and C-22 of sterol skeleton which is rarely found in nature. Meanwhile, compound 2 could be form by oxidative breakdown C-20/C-22 bonding of a furostane-type saponin. Compounds 1–3 showed weak cytotoxicity against HepG2 cell line with IC50 values of 55.7 ± 1.5, 48.1 ± 2.2, and 78.3 ± 2.4 μM, respectively.