Biological effects of insulin on murine melanoma cells and fish erythrophoroma cells: A comparative study

Insulin is the hormone that plays an essential role in metabolism and mitosis of normal and tumor cells, exerting its pleiotropic effects through binding to specific membrane receptors and promoting the phosphorylation of tyrosine residues of the receptor itself and of other components of the signaling pathway. The aim of this study was to investigate the effects of insulin on melanogenesis and cell growth in three different cell lines: the goldfish GEM-81 erythrophoroma cells (undifferentiated and differentiated with 1.5% dimethylsulfoxide-DMSO), and the murine B16F10 and Cloudman S91 melanoma cells. Undifferentiated GEM-81 and B16F10 cells responded to insulin with a small increase of cell proliferation, whereas S91 cells responded with a decrease of growth. In the two mammalian cell lines, and in DMSO-differentiated GEM-81 cells, the hormone strongly inhibited melanogenesis, by decreasing tyrosinase activity. In undifferentiated GEM-81 cells, insulin had no effect on tyrosinase activity. An increase in the tyrosine phosphorylation status of pp 185 (insulin receptor substrate 1 and 2-IRS-1/2) phosphorylation degree was observed in S91 mouse melanoma and in differentiated GEM-81 erythrophoroma cells, suggesting that this specific protein was maintained during transformation process and participates in insulin signaling. Our results imply an ancient and diverse history of the insulin signaling system in vertebrate pigment cells. (C) 2008 Elsevier Inc. All rights reserved.

Effect of 3,4-ethylenedioxy-extension of thiophene core on the DNA/RNA binding properties and biological activity of bisbenzimidazole amidines

Novel bisbenzimidazoles (4-6), characterized by 3,4-ethylenedioxy-extension of thiophene core, revealed pronounced affinity and strong thermal stabilization effect toward ds-DNA. They interact within ds-DNA grooves as dimmers or even oligomers and agglomerate along ds-RNA. Compounds 4-6 have shown moderate to strong antiproliferative effect toward panel of eight carcinoma cell lines. Compound 5 displayed the best inhibitory potential and in equitoxic concentration (IC(50) = 1 x 10 (6) M) induced accumulation of cells in G2/M phase after 48 h of incubation. Fluorescence microscopy showed that 5 entered into live HeLa cells within 30 min, but did not accumulate in nuclei even after 2.5 h. Compound 5 inhibited the growth of Trypanosome cruzi epimastigotes (IC(50) = 4.3 x 10 (6) M). (C) 2009 Elsevier Ltd. All rights reserved.

Biological effects of anionic meso-tetrakis (para-sulfonatophenyl) porphyrins modulated by the metal center. Studies in rat liver mitochondria

In this paper, we present a study about the influence of the porphyrin metal center and mesa ligands on the biological effects of meso-tetrakis porphyrins. Different from the cationic meso-tetrakis 4-N-methyl pyridinium (Mn(III)TMPyP), the anionic Mn(III) meso-tetrakis (para-sulfonatophenyl) porphyrin (Mn(III)TPPS4) exhibited no protector effect against Fe(citrate)-induced lipid oxidation. Mn(III)TPPS4 did not protect mitochondria against endogenous hydrogen peroxide and only delayed the swelling caused by tert-BuOOH and Ca(2+). Fe(III)TPPS4 exacerbated the effect of the tert-BuOOH, and both porphyrins did not significantly affect Fe(II)citrate-induced swelling. Consistently, Fe(III)TPPS4 predominantly promotes the homolytic cleavage of peroxides and exhibits catalytic efficiency ten-fold higher than Mn(III)TPPS4. For Mn(III)TPPS4, the microenvironment of rat liver mitochondria favors the heterolytic cleavage of peroxides and increases the catalytic efficiency of the manganese porphyrin due to the availability of axial ligands for the metal center and reducing agents such as glutathione (GSH) and proteins necessary for Compound II (oxomanganese IV) recycling to the initial Mn(III) form. The use of thiol reducing agents for the recycling of Mn(III)TPPS4 leads to GSH depletion and protein oxidation and consequent damages in the organelle. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Synthesis, characterization, crystal structure, and biological studies of vanadium complexes with glycolic acid

Synthesis, characterization, crystal structure, and biological studies of two complexes with glycolic acid are described. The solid complexes were formulated as K2[VO(C2H2O3)(C2H3O3)2] H2O (1) and K2[{VO2(C2H2O3)}2] (2) and characterized by X-ray studies, Fourier transform infrared spectroscopy (FTIR), Electron paramagnetic resonance (EPR), and magnetic susceptibility. Conversion of 1 to 2 was studied in aqueous solution by UV-Vis spectroscopy and in the solid state by diffuse reflectance spectroscopy. Complex 2 contains dinuclear [{VO2(C2H2O3)}2]2- anions in which glycolate(2-) is a five-membered chelating ring formed by carboxylate and -hydroxy groups. The geometry around the vanadium in 2 was interpreted as intermediate between a trigonal bipyramid and a square pyramid. Vanadium(IV) is pentacoordinate in 1 as a distorted square pyramid. Complex 1 contains a vanadyl group (V=O) surrounded by two oxygens from deprotonated carboxylate and hydroxy groups forming a five-membered ring. Two oxygens from different glycolates(1-) are bonded to the (V=O) also. Biological analysis for potential cytotoxic effects of 1 was performed using Human Cervix Adenocarcinoma (HeLa) cells, a human cervix adenocarcinoma-derived cell line. After incubation for 48 h, 1 causes 90 and 95% of HeLa cells death at 20 and 200 mol L-1, respectively.

STABILITY ANALYSIS WITH APPLICATIONS OF A TWO-DIMENSIONAL DYNAMICAL SYSTEM ARISING FROM A STOCHASTIC MODEL FOR AN ASSET MARKET

We analyze the stability properties of equilibrium solutions and periodicity of orbits in a two-dimensional dynamical system whose orbits mimic the evolution of the price of an asset and the excess demand for that asset. The construction of the system is grounded upon a heterogeneous interacting agent model for a single risky asset market. An advantage of this construction procedure is that the resulting dynamical system becomes a macroscopic market model which mirrors the market quantities and qualities that would typically be taken into account solely at the microscopic level of modeling. The system`s parameters correspond to: (a) the proportion of speculators in a market; (b) the traders` speculative trend; (c) the degree of heterogeneity of idiosyncratic evaluations of the market agents with respect to the asset`s fundamental value; and (d) the strength of the feedback of the population excess demand on the asset price update increment. This correspondence allows us to employ our results in order to infer plausible causes for the emergence of price and demand fluctuations in a real asset market. The employment of dynamical systems for studying evolution of stochastic models of socio-economic phenomena is quite usual in the area of heterogeneous interacting agent models. However, in the vast majority of the cases present in the literature, these dynamical systems are one-dimensional. Our work is among the few in the area that construct and study analytically a two-dimensional dynamical system and apply it for explanation of socio-economic phenomena.

Structure and Applications of a Rhamnolipid Surfactant Produced in Soybean Oil Waste

Soybean oil soapstock was utilized as an alternative carbon source for the production of rhamnolipids by Pseudomonas aeruginosa LBI strain. The chemical composition and properties of the rhamnolipid mixture obtained were determined to define its potential applications. The chemical characterization of the rhamnolipid has revealed the presence of ten different homologues. The monorhamnolipid RhaC(10)C(10) and the dirhamnolipid Rha(2)C(10)C(10) were the main components of the mixture that showed predominance of 44% and 29%, respectively, after 144-h of cultivation. The biosurfactant was able to form stable emulsions with several hydrocarbons and showed excellent emulsification for soybean oil and chicken fat (100%). The rhamnolipid removed 67% of crude oil present in sand samples and presented antimicrobial activity against Bacillus cereus and Mucor miehei at 64 mu g/mL and inhibition of Neurospora crassa, Staphylococcus aureus, and Micrococcus luteus at 256 mu g/mL. The results demonstrated that the rhamnolipid produced in soybean oil soapstock can be useful in environmental and food industry applications.

Synthesis, characterization and biological analysis of the complex [VO(Hdhp)(2)] (H(2)dhp=2,3-dihydroxypyridine)

A new vanadium (IV) complex with the monoanion of 2,3-dihydroxypyridine (H(2)dhp), or 3-hydroxy-2(1H)-pyridone, was synthesized, characterized by physicochemical techniques and tested biologically. The EPR data for the [VO(Hdhp)(2)] complex in DMF are: g(x) = 1.9768, g(y) = 1.9768 and g(z) = 1.9390; A values (10(-4) cm(-1)): A(x), 59.4; A(y//), 59.4; A(z), 171.0. The vV=O band in the IR spectrum of the complex is at 986 cm(-1). The complex is paramagnetic, with mu(eff) = 1.65 BM (d(1), spin-only) at 25 degrees C. The irreversible oxidation process [V(V)/V(IV)] of the [VO(Hdhp)(2)] complex, as revealed in a cyclic voltammogram, occurs at 876 mV. The calculated molecular structure of [VO(Hdhp)(2)] shows the vanadium(IV) center in a distorted square pyramidal environment, with the oxo ligand in the apical position and the oxygen donor atoms of the Hdhp ligands in the basal positions. The ability of [VO(Hdhp)(2)] to mimic insulin, and its toxicity to hepato-biliary functions, were investigated in streptozotocin-induced diabetic rats and it was concluded that the length of treatment and the amount of [VO(Hdhp)(2)] administered were effective in reducing experimental diabetes.

Synthesis, Structural Characterization, and Biological Evaluation of Oxorhenium(V) Complexes with a Novel Type of Thiosemicarbazones Derived from N-[N `,N `-Dialkylamino(thiocarbonyl)]benzimidoyl Chlorides

Reactions of N-[N`,N`-diethylamino(thiocarbonyl)]benzimidoyl chloride with 4,4-dialkylthiosemicarbazides give a novel class of thiosemicarbazides/thiosemicarbazones, H(2)L, which causes a remarkable reduction of cell growth in in vitro experiments. These strong antiproliferative effects are also observed for oxorhenium(V) complexes of the general composition [ReOCl(L)], which are formed by reactions of the potentially tridentate ligands with (NBu(4))[ReOCl(4)]. A systematic substitution of the alkyl groups in the thiosemicarbazone building blocks of the ligands do not significantly influence the biological activity of the metal complexes, while the replacement of the chloro ligand by a PPh(3) ligand (by the replacement of the oxo unit by a nitrido ligand) completely terminated the cytotoxicity of the metal complexes.