DTA0100, dual topoisomerase II and microtubule inhibitor, evades paclitaxel resistance in P-glycoprotein overexpressing cancer cells

The efficacy of microtubule targeting agents in cancer treatment has been compromised by the development of drug resistance that may involve both, P-glycoprotein overexpression and the changes in beta-tubulin isoforms' expression. The anti-Topoisomerase II activity of methyl 4-((E)-2-(methoxycarbonyl)vinyloxy)oct-2-ynoate (DTA0100) was recently reported. Herein, we further evaluated this propargylic enol ether derivative and found that it exerts inhibitory effect on tubulin polymerization by binding to colchicine binding site. DTA0100 mitotic arrest properties were investigated in two multi-drug resistant cancer cell lines with P-glycoprotein overexpression (colorectal carcinoma and glioblastoma). The sensitivity of multi-drug resistant cancer cell lines to DTA0100 was not significantly changed in contrast to microtubule targeting agents such as paclitaxel, vinblastine and colchicine. DTA0100 clearly induced microtubule depolymerization, leading to disturbance of cell cycle kinetics and subsequent apoptosis. The fine-tuning in beta-tubulin isoforms expression observed in multi drug resistant cancer cells may influence the efficacy of DTA0100. Importantly, DTA0100 blocked the Pglycoprotein function in both multi-drug resistant cancer cell lines without inducing the increase in Pglycoprotein expression. Therefore, DTA0100 acting as dual inhibitor of Topoisomerase II and microtubule formation could be considered as multi-potent anticancer agent. Besides, it is able to overcome the problem of drug resistance that emerges in the therapeutic approaches with either Topoisomerase II or microtubule targeting agents.Related to published version: [https://imagine.imgge.bg.ac.rs/handle/123456789/1079]This is the peer reviewed version of the paper: Podolski-Renić, A., Banković, J., Dinić, J., Rios-Luci, C., Fernandes, M. X., Ortega, N., Kovačević Grujičić, N., Martin, V. S., Padron, J. M., & Pesić, M. (2017). DTA0100, dual topoisomerase II and microtubule inhibitor, evades paclitaxel resistance in P-glycoprotein overexpressing cancer cells. European Journal of Pharmaceutical Sciences, 105, 159–168. [https://doi.org/10.1016/j.ejps.2017.05.011

Preliminary data on the reproductive characteristics and diet in an insular population of the lacertid lizard Algyroides nigropunctatus

We present basic data on the female reproductive traits and diet of the lacertid lizard Algyroides nigropunctatus from Bisage island in Lake Skadar (Montenegro) in late spring. Individual females commonly laid clutches of three (range 2 - 5) eggs with an average mass of 0.40 g. At least two clutches were produced in a breeding season. The female body size had no effect on clutch and egg size. There was no evidence of the predicted trade-off between egg size and clutch size. The diet was composed of various types of invertebrates, basically small arthropods, and also small amounts of plant material. Araneae and Coleoptera were the most common and the most important food items.Serbian Ministry of Education and Science [173043

Effect of Electrodeposition Current Density on the Microstructure and Magnetic Properties of Nickel-cobalt-molybdenum Alloy Powders

Nanostructured nickel-cobalt-molybdenum alloy powders were electrodeposited from an ammonium sulfate bath. The powders mostly consist of an amorphous phase and a very small amount of nanocrystals with an mean size of less than 3 nm. An increase in deposition current density increases the amorphous phase percentage, the density of chaotically distributed dislocations and internal microstrains in the powders, while decreasing the mean nanocrystal size. The temperature range over which the structural relaxation of the powders deposited at higher current densities occurs is shifted towards lower temperatures. A change in relative magnetic permeability during structural relaxation is higher in powders deposited at higher current densities. Powder crystallization takes place at temperatures above 700 degrees C. The formation of the stable crystal structure causes a decrease in relative magnetic permeability

The effect of extremely low-frequency magnetic field on motor activity of rats in the open field

Exposure to extremely low-frequency magnetic field (ELF-MF, 50 Hz, 0.5 mT) for seven days did not change spontaneous motor activity of rats in the open field compared to sham-exposed animals. Pre-exposure to ELF-MF decreased locomotor and stereotypic activity induced by amphetamine (1.5 mg/kg body weight) and accordingly increased the resting time compared to sham-exposed and amphetamine-treated rats. Vertical activity (rearing) of these two groups was similar. Our results indicate that ELF-MF has different effects on some parameters of amphetamine-induced motor activity, probably due to brain region-specific effects on catecholaminergic systems responsible for movement control.nul

The effects of exposure to extremely low-frequency magnetic field and amphetamine on the reduced glutathione in the brain

Continuous exposure to extremely low-frequency magnetic field (ELF-MF, 50 Hz, 0.5 mT) alone and combined with D-amphetamine (1.5 mg/kg) affected the reduced glutathione content in brain regions of rats. Compared to sham-exposed rats, the glutathione content in the forebrain cortex of the ELFMF-exposed rats decreased (P < 0.001), but this reverted after giving amphetamine upon ELF-MF exposure. In this group, the glutathione content was increased in the brain stem and cerebellum (P < 0.05 compared to the shame-exposed, ELM-MF-exposed, and amphetamine-treated groups). It is suggested that biogenic monoamines are involved in the reduced glutathione changes observed. The changes are not uniform in the brain regions examined.nul

Persistent economic divergence and institutional dysfunction in post-communist economies: an alternative synthesis

This paper seeks to explain the continuing lack of economic convergence and the persistence of market dysfunctionality, or wild capitalism, in post Communist transformation. An overview of key statistics on economic convergence and market failure are presented. The paper then analyses the causes of malaise through the lens of institutionalist and radical perspectives. In doing so key data is assembled and presented from documents of the international financial institutions and other agencies monitoring crime and corruption. The paper concludes that rather than encourage convergence and tame dysfunctionality, neoliberalism and its offspring of labour market reform has created the conditions for continuing economic divergence and for wild capitalism to survive and thrive

The effects of exposure to extremely low-frequency magnetic field and amphetamine on the reduced glutathione in the brain

Continuous exposure to extremely low-frequency magnetic field (ELF-MF, 50 Hz, 0.5 mT) alone and combined with D-amphetamine (1.5 mg/kg) affected the reduced glutathione content in brain regions of rats. Compared to sham-exposed rats, the glutathione content in the forebrain cortex of the ELFMF-exposed rats decreased (P < 0.001), but this reverted after giving amphetamine upon ELF-MF exposure. In this group, the glutathione content was increased in the brain stem and cerebellum (P < 0.05 compared to the shame-exposed, ELM-MF-exposed, and amphetamine-treated groups). It is suggested that biogenic monoamines are involved in the reduced glutathione changes observed. The changes are not uniform in the brain regions examined.nul

Effects of extremely low-frequency magnetic field in the brain of rats

An extremely low-frequency magnetic field (50 Hz, 0.5 mT) was used to investigate its possible effect on the brain of adult male Wistar rats following a 7-day exposure. The control rats were sham-exposed. Superoxide dismutase activities and production Of Superoxide radicals, lipid peroxidation, and nitric oxide were examined in the frontal cortex, striatum, basal forebrain, hippocampus, brainstem, and cerebellum. Significantly increased superoxide radical contents were registered in all the structures examined. Production of nitric oxide, which can oppose superoxide radical activities, was significantly increased in some structures: the frontal cortex, basal forebrain, hippocampus, and brainstem. Augmentation of lipid peroxydation was also observed, with significance only in the basal forebrain and frontal cortex, in spite of the significantly increased superoxide dismutase activities and nitric oxide production in the basal forebrain, and increased production of nitric oxide in the frontal cortex. The results obtained indicate that a 7-day exposure to extremely low-frequency magnetic field can be harmful to the brain, especially to the basal forebrain and frontal cortex due to development of lipid peroxidation. Also, high production of superoxide anion in all regions may compromise nitric oxide signaling processes, due to nitric oxide consumption in the reaction with the superoxide radical. (C) 2005 Elsevier Inc. All rights reserved.nul