Cytotoxic and antiproliferative effects of thymoquinone on rat C6 glioma cells depend on oxidative stress.

Thymoquinone (TQ) is a highly perspective chemotherapeutic agent against gliomas and glioblastomas because of its ability to cross the blood-brain barrier and its selective cytotoxicity for glioblastoma cells compared to primary astrocytes. Here, we tested the hypothesis that TQ-induced mild oxidative stress provokes C6 glioma cell apoptosis through redox-dependent alteration of MAPK proteins. We showed that low concentrations of TQ (20-50 µM) promoted cell-cycle arrest and induced hydrogen peroxide generation as a result of NADH-quinone oxidoreductase 1-catalyzed two-electron reduction of this quinone. Similarly, low concentrations of TQ efficiently conjugated intracellular GSH disturbing redox state of glioma cells and provoking mitochondrial dysfunction. We demonstrated that high concentrations of TQ (70-100 µM) induced reactive oxygen species generation due to its one-electron reduction. TQ provoked apoptosis in C6 glioma cells through mitochondrial potential dissipation and permeability transition pore opening. The identified TQ modes of action on C6 glioma cells open up the possibility of considering it as a promising agent to enhance the sensitivity of cancer cells to standard chemotherapeutic drugs.

THE INFLUENCE OF QUERCETIN ON THE HEPATIC DIFFERENTIATION OF HUMAN ADIPOSE-DERIVED MESENCHYMAL STEM CELLS.

The human adipose-derived mesenchymal stem cells was shown to be hepatic differentiated under influence of inductor factors. The differentiation of MSCs was induced by fibroblast growth factor-4, hepatocyte growth factor, oncostatin M and dexamethasone. The influence of quercetin on the hepatic differentiation of MSCs in culture was investigated. The adding quercetin into induction medium (1 or 10 mmol/l) enhanced the manifestation of signs of hepatic differentiation MSCs such as urea secretion, cytokeratin 19 and a-fetoprotein synthesis. Quercetin modulating action on the CYP1A ­ cytochrome P450 activity in differentiated cells was found. MSCs which was differentiated in the presence of quercetin had a higher viability and resistance to oxidative stress.

[The influence of fibroblast growth factor (FGF2) on cardiomyocytes differentiation of mesenchymal stem cells of bone marrow ex vivo].

The influence of FGF2 on the efficiency of cardiomyocytes differentiation of mesenchymal stem cells (MSC) of bone marrow induced by 5-azacetidine (5-aza) was studied. The effect of FGF2 developing by the 14th day after the combined action of a differentiating agent and growth factor was manifested in an increase in Mef2A, Mef2D and gene transcription and a rise of ionized Ca2+ concentration in cytoplasm keeping cell viability and proliferation activity. In the presence of FGF2 this approach provided cardiomyogenesis and the increase in the formation of early precursors of cardiomyocytes.

[Photodamage to spores of Fusarium fungi, sensitized by protoporphyrin IX].

The influence of photodynamic action with protoporphyrin IX as a sensitizer on the state of the components of hydrated spores of Fusarium fungi and germination of conidia in growth medium was investigated. It was shown, that protoporphyrin IX in micromole concentrations sensitizes the photooxidation of proteins and lipids from hydrated spores of Fusarium poae and Fusarium culmorum under illumination of their suspensions in doses of 50 - 200 kJ/m2. It was found that the photosensitized oxidation of cellular components leads to the disturbance of conidium membrane permeability and inhibition of spore germination during their subsequent cultivation in growth medium.

[The influence of halogenorganic compounds on radiation induced damage of rat eye lens components]. / Vliianie galogenorganicheskikh soedinenii na radiatsionno-indutsiruemye povrezhdeniia komponentov khrustalika glaza krysy.

In experiments with white rats the damages of eye lens components of the animals are investigated under combined action of halogenorganic compounds (chloroform and sodium trichloroacetate) and radiation (137Cs) in vivo. It was shown that the injection of these compounds into animals amplifies the radiation-induced oxidation of eye lens components. The effect is manifested in the increase in the content of chromophors with fluorescence in the visible range and products of lipid peroxidation, the decrease in the amount of reduced glutathione. The data support the increased risk of development of radiation-induced cataract in the conditions of tehnogenic pollution of the environment.

[Mechanisms of enhancing UV lihg-induced lipid peroxidation in isolated erythrocyte membranes by organohalogen compounds]. / Mekhanizmy usileniia galogenorganicheskimi soedineniiami indutsiruemogo UF-svetom perekisnogo okisleniia lipidov v izolirovannykh membranakh éritrotsitov.

It was found that a number of halogen-containing compounds (chloroform, carbon tetrachloride, difluorodichloromethane, sodium trichloroacetate) enhance the lipid peroxidation induced by UV light (265-300 nm) in isolated erythrocyte membranes. It was shown that the enhancement is realized with participation of excited states of membrane protein tryptophanyls, which may induce the reduction of halogen-containing compounds with formation of radicals having a high oxidative activity. Moreover, halogen-containing compounds decrease the antioxidant protection of membrane lipids owing to an increase in quantum yield of alpha-tocopherol photodestruction.

[Effects of halogen derivative hydrocarbons on radiation damage of biological membranes]. / Vliianie galogenproizvodnykh uglevodorodov na radiatsionnye povrezhdeniia biologicheskikh membran.

Sharp increase of radiation-induced damages of isolated erythrocyte membrane lipids and proteins upon irradiation in presence of some halogen derivative hydrocarbon are shown. On chloroform and CCl4 examples it is shown that marked effects displayed under relatively low (submillimoles) concentrations and radiation doses that induced only insignificant oxidative membrane damages in absence of modifiers. The data are received which evidenced in favour of decisive role in these processes of halogenated organic radicals forming under one-electron reduction of halogen derivative hydrocarbons by hydrated electrons.

[Formation and photosensitizing activity of protein tryptophanile photochemical breakdown products in isolated erythrocyte membranes]. / Obrazovanie i fotosensibiliziruiushchaia aktivnost' produktov fotokhimicheskogo razrusheniia triptofanilov belkov v izolirovannykh éritrotsitarnykh membranakh.

Modification of photochemical processes in protein tryptophaniles of isolated erythrocyte membranes by chloroform was shown. It is established that formed in the presence of chloroform photoproducts are able to act as "internal" sensitizers of oxidation of membrane proteins and lipids when illuminated by UV light of ecological range.