[Influence of N-alkynylaminosteroids on mitochondria function and autophagy in glioma cells]. / Vliianie N-alkinilaminosteroidov na funktsionirovanie mitokhondrii i protsessy autofagii v kletkakh gliomy.

In this work we examined the synthesized N-alkynyl-17-aminosteroids and N-alkynyl-20-aminosteroids (based on dehydroepiandrosterone and pregnenolone, respectively) for their effect on C6 rat glioma cell functions. At 10 µM, the compounds had an insignificant effect on C6 glioma mitochondrial membrane potential, but increased cell autophagy by 70-90%, comparable to the known autophagy inducer dexamethasone. Docking simulations predict a potential high-affinity interaction between N-alkynylaminosteroids and Keap1 and the Hedgehog pathway protein, Smoothened, which are involved in autophagy regulation. The possible mechanisms of observed processes are discussed.

Single-walled carbon nanotubes as a photo-thermo-acoustic cancer theranostic agent: theory and proof of the concept experiment.

Theranostics is the emerging field of medicine that uniquely combines diagnostic techniques and active agents to diagnose and treat medical conditions simultaneously or sequentially. Finding a theranostic agent capable to cure the affected cells and being safe for the healthy ones is the key for successful treatment. Here, we demonstrate that agglomerated single-walled carbon nanotubes (SWCNTs) are promising theranostic agent that enables photo-activated 'cold' destruction of the cancer cells keeping their environment alive. The absorption of picosecond pulses by SWCNT agglomerates results in the mechanical (due to photoacoustic effect) rather than photothermal cancer cell destruction, which was visualized by micro-Raman and ultrafast near-infrared CARS. The developed theoretical model allows us to distinguish photothermal, photoacoustic, and photothermoacoustic regimes of the cancer cell destruction, and also to optimize SWCNT-based theranostics recipe.

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.

Redox regulation of mitochondrial functional activity by quinones.

Quinones are among the rare compounds successfully used as therapeutic agents to correct mitochondrial diseases and as specific regulators of mitochondrial function within cells. The aim of the present study was to elucidate the redox-dependent effects of quinones on mitochondrial function. The functional parameters [respiratory activity, membrane potential, and reactive oxygen species (ROS) generation] of isolated rat liver mitochondria and mitochondria in intact cells were measured in the presence of eight exogenously applied quinones that differ in lipophilicity and one-electron reduction potential. The quinones affected the respiratory parameters of mitochondria, and dissipated the mitochondrial membrane potential as well as influenced (either decreased or enhanced) ROS generation, and restored the electron flow during electron transport chain inhibition. The stimulation of ROS production by juglone and 2,5-di-tert-butyl-1,4-benzoquinone was accompanied by a decrease in the acceptor control and respiration control ratios, dissipation of the mitochondrial membrane potential and induction of the reverse electron flow under succinate oxidation in isolated mitochondria. Menadione and 2,3,5-trimethyl-1,4-benzoquinone, which decreased the mitochondrial ROS generation, did not affect the mitochondrial potential and, vice versa, were capable of restoring electron transport during Complex I inhibition. In intact C6 cells, all the quinones, except for coenzyme Q10, decreased the mitochondrial membrane potential. Juglone, 1,4-benzoquinone, and menadione showed the most pronounced effects. These findings indicate that quinones with the reduction potential values E1/2 in the range from -99 to -260 mV were effective redox regulators of mitochondrial electron transport.