Antioxidant and anticancer properties of leaves and seed cones from European yew (Taxus baccata L.)

Plant extracts of the leaves and seed cones of European yew Taxus baccata L. (Taxaceae) were analyzed for total phenolic content, flavonoid concentrations, antioxidant and anticancer properties (cytotoxic and proapoptotic activity). The total phenolic content ranged between 8.23 and 210.01 mg Ga/g, with the IC 50 values for antioxidant activity between 25.24 and 533.66 μg/ml. The MTT test showed that the methanolic extract of leaves had better activity on HCT-116 cells than the extract of seed cones, with IC 50 values of 14.3 for 24 h and 4.59 for 72 h. The MDA-MB-231 cell line displayed significantly lower sensitivity to both extracts as compared to the HCT-116 cell line. Microscopic examination indicated that the extracts induced apoptosis in both cell lines. These results suggest that T. baccata leaves and seed cones are a potential source of phenolic compounds, especially flavonoids, as natural antioxidant, cytotoxic and strong proapoptotic substances of high value

Bioinformatics online support for bioactive substances cytotoxicity testing and their statistical analysis

Preclinical in vitro/in vivo testing is the first step in discovery of anticancer medicines, among others evaluation of cytotoxic activity of bioactive substances (BAS) on various human normal and cancer cell lines. Cytotoxicity expressed as IC50 value (a dose that inhibits 50% of cell growth) is one of the most commonly used parameter for comparable analysis of activity between different substances. This study includes examination of number of BAS and their results for cytotoxic activity obtained in the Laboratory for cell and molecular biology (LCMB) that require various statistical and computational techniques for proper effective analysis. In order to improve experimental data analysis, make it faster, more effective, error proof with secure online data repository, a Web application with LCMB IC50 database was developed as a useful research tool acting as a leverage for scientific data processing requirements. Analysis includes cytotoxic effects of chemical and natural BAS (IC50 values) on HCT-116, SW-480, MDA-MB-231, and MRC-5 cell lines. Generally, it can be concluded that BAS of different origin, chemical or natural, have various cytotoxic effects and cause different cell line sensitivity, which is presented and discussed. This paper presents developed SQL database-centric Web application with remote user-friendly data management for a biology researcher user type profile. Data processing in this article can be useful for a further overlook and testing of cytotoxic substances.Publishe

Altered apoptosis and biotransformation signaling in HCT-116 colorectal carcinoma cells induced by Teucrium chamaedrys L. extract

The aim of this study was an investigation of pro-apoptotic activity of methanol extract from T. chamaedrys, a more detailed determination of the signal molecules activated in the process of apoptosis, and effects on mRNA expression of enzymes involved in biotransformation (CYP1A1 and GSTP1) and membrane transporter, MRP-2 in HCT-116 colorectal carcinoma cells. The results show pronounced proapoptotic activity of T. chamaedrys extract, due to activation of both extrinsic and intrinsic pathways. The death receptor associated signaling pathway was activated in HCT-116 following treatment by T. chamaedrys, via increased Fas receptor expression and activity of caspase 8. Activation of caspase 9 suggests that mitochondrial signalling also has an impact. The extract reduced mRNA expression of GSTP1 and MRP-2 genes, as one of the causes of multi drug resistance in cancer cells. Observed results offer the possibility for the use of T. chamaedrys extract in the context of cancer prevention and therapy.Publishe

Effects of royal jelly on energy status and expression of apoptosis and biotransformation genes in normal fibroblast and colon cancer cells

Royal jelly is natural bee product, traditionally used in medicine for antitumor, anti-inflammatory, antioxidant, antibiotic and many other beneficial properties. The aim of this study was to determine biological effects of royal jelly samples originating from Serbia on normal human fibroblast (MRC-5) and colorectal cancer (HCT-116 and SW-480) cells. MTT cell viability assay was used to determine cytotoxic activity, and NBT test was used for determination of superoxide anion radical concentration. Parameters of cell energy status were determined using LDH and ATP colorimetric methods. Relative expression of mRNA of apoptosis and biotransformation genes was monitored by qPCR method. Royal jelly affected cell viability, caused oxidative stress appearance and elevated parameters of energy status in cancer cell lines. The relative expression of genes whose proteins are included in biotransformation of xenobiotics were changed with notable suppression of CYP1A1, while increased expression of apoptosis genes was noted in tested cell lines. Royal jelly demonstrated cell selective effect and could be prospective in anticancer therapy.Publishe

Studies of the stability, nucleophilic substitution reactions, DNA/BSA interactions, cytotoxic activity, DFT and molecular docking of some tetra- and penta-coordinated gold(iii) complexes

Two gold(III) complexes, square-planar [Au(DPP)Cl2]+(1) and distorted square-pyramidal [Au(DMP)Cl3] (2) (where DMP = 2,9-dimethyl-1,10-phenanthroline and DPP = 4,7-diphenyl-1,10-phenanthroline), were studied by different experimental methods. Their stability in water and in buffer solution (25 mM Hepes, 30 mM NaCl, pH = 7.2) was investigated by UV-Vis spectroscopy while their redox stability is confirmed by CV. Substitution reactions between complexes 1 and 2, and biologically relevant ligands, such as thiourea (Tu), guanosine-5′-monophosphate (5′-GMP), glutathione (GSH) and L-methionine (L-Met), were studied by a stopped-flow technique, under the pseudo-first order conditions as a function of ligand concentration and temperature. According to the values of the activation parameters, all studied reactions followed an associative substitution mechanism. DNA binding studies of complexes 1 and 2 were performed by UV-Vis and fluorescence spectroscopy and viscosity measurements, as well as interactions with bovine serum albumin (BSA). Density functional theory (DFT) was implemented in order to analyse the wave function of the optimized structures to get better insight into the binding interactions between the inert ligands and gold(III) center. The experimental results of binding studies with DNA and BSA were simulated and compared by performing a molecular docking study. All results demonstrate the strong connection between the reactivity of the complexes toward biologically important targets and their structural and electronic characteristics. The cytotoxic activity of complexes 1 and 2 against different cell lines (MDA-MB-231, HCT-116, and HaCaT) was evaluated 24 and 72 h after treatments. The results indicate reduced viability of cell lines in a time- and dose-dependent manner.Accepted for publishin

Alteration of oxidative stress parameters in red blood cells of rats after chronic in Vivo treatment with cisplatin and selenium

In this study we evaluated the possible protective effects of selenium (Se) on hematological and oxidative stress parameters in rats chronically treated with cisplatin (cisPt). Four groups of Wistar albino rats were examined: a control, untreated rats (I), rats treated with Se (II), rats treated with cisPt (III), and rats treated with Se and cisPt (IV). All animals were treated for 5 days successively and killed 24 h after the last treatment. Hematological and oxidative stress parameters were followed in whole blood and red blood cells (RBC). Results showed that the chronic application of Se was followed by a higher number of reticulocytes and platelets, increased lipid peroxidation and GSH content in the RBC. Cisplatin treatment induced depletion of RBC and platelet numbers and an elevation of the superoxide anion, nitrites and glutathione levels. Se and cisPt co-treatment was followed by an elevation of the hematological parameters and the recovery of the glutathione status when compared to the control and cisPt-treated rats

The EU enlargement and income convergence: Central and Eastern European countries vs. Western Balkan countries

© 2018, Cracow University of Economics. All rights reserved. Objective: This article analyses the stochastic convergence of income per capita between the Western Balkan (WB) and the Central and Eastern European (CEE) countries compared to developed EU countries (EU15). Research Design & Methods: Stochastic convergence implies that all shocks in country’s income relative to the average income of the group are only temporary. In order to test stochastic convergence, the tests of the unit root were used. The Augmented Dickey-Fuller (ADF) test is supplemented with the Zivot-Andrews (ZA) unit root test, which allows for the structural breaks in time series of income per capita. Findings: Results confirm the existence of stochastic convergence of income per capita toward the EU15 average in the cases of the Czech Republic, Slovakia, Poland, Slovenia, Estonia, Latvia and Romania. Income convergence is not found in the case of the Western Balkan countries. Implications & Recommendations: While income convergence toward the EU15 average level was found in the case of 7 CEE countries, it was not found in the case of any WB country. This could be a proof of the importance of further support to reforms in the Western Balkan countries. Contribution & Value Added: The scientific contribution of the article is reflected in the fact that the existing literature dealing with income convergence of the Western Balkan countries toward the income of the EU15 countries is still very limited in number, as is the number of studies that compare convergence of income per capita toward the EU15 between the Western Balkan and CEE countries

Combinatorics of unavoidable complexes

© 2019 Elsevier Ltd The partition number π(K) of a simplicial complex K⊆2[n] is the minimum integer k such that for each partition A1⊎…⊎Ak=[n] of [n] at least one of the sets Ai is in K. A complex K is r-unavoidable if π(K)≤r. Simplicial complexes with small π(K) are important for applications of the “constraint method” (Blagojević et al., 2014) and serve as an input for the “index inequalities” (Jojić et al., 2018), such as (1.1). We introduce a “threshold characteristic” ρ(K) of K (Section 3) and define a fractional (linear programming) relaxation of π(K) (Section 4), which allows us to systematically generate interesting examples of r-unavoidable complexes and pave the way for new results of Van Kampen–Flores–Tverberg type

Biotransformation and nitroglycerin-induced effects on antioxidative defense system in rat erythrocytes and reticulocytes

The effects of nitroglycerin (glyceryl trinitrate -GTN) are mediated by liberated nitric oxide (NO) and formed reactive nitrogen species, which induces oxidative stress during biotransformation in red blood cells (RBCs). The aim of this study was to evaluate effects of GTN on antioxidative defense system (AOS) in rat erythrocytes (without) and reticulocytes (with functional mitochondria). Rat erythrocyte and reticulocyte-rich RBC suspensions were aerobically incubated (2 h, 37°C) without (control) or in the presence of different concentrations of GTN (0.1-1.5 mM). After incubation, concentrations of non-enzymatic components of AOS, activities of antioxidative enzymes and oxidative pentose phosphate (OPP) pathway activity were followed in RBC suspensions. In rat reticulocytes, GTN decreased the activity of mitochondrial MnSOD and increased the activity of CuZnSOD. In rat RBCs, GTN induced increase of Vit E concentration (at high doses), but decreased glutathione content and activities of all glutathione-dependent antioxidative enzymes; the OPP pathway activity significantly increased. GTN biotransformation and induction of oxidative stress were followed by general disbalance of antioxidative capacities in both kinds of RBCs. We suggest that oxidative stress, MnSOD inhibition and depletion of glutathione pool in response to GTN treatment lead to decreased bioavailability of NO after GTN biotransformation in rat reticulocytes

Cytotoxic, antimigratory, pro-and antioxidative activities of extracts from medicinal mushrooms on colon cancer cell lines

Methanol extracts of five commercially available mushroom species (Phellinus linteus (Berk. et Curt) Teng, Cordyceps sinensis (Berk.) Sacc., Lentinus edodes (Berk.) Pegler, Coprinus comatus (O. F. Müll.) Pers. and Ganoderma lucidum (Curtis) P. Karst), traditionally used as anticancer agents, were evaluated in vitro for their total phenol and flavonoid contents, cytotoxic and antimigratory activities and antioxidant/prooxidant effects on colon cancer cell lines (HCT-116 and SW-480). Spectrophotometric methods were used for the determination of total phenol content, flavonoid concentrations and DPPH activity of the extracts. Cytotoxic activity was measured by the MTT assay. The antimigratory activity of extracts was determined using the Transwell assay and immunofluorescence staining of ß-catenin. The prooxidant/antioxidant status was followed by measuring the superoxide anion radical (O2•-), nitrite and reduced glutathione (GSH) concentrations. Our results show that the highest phenolic and flavonoid content was found in P. linteus, and its DPPH-scavenging capacity was significantly higher than in other samples. The P. linteus extract significantly decreased cell viability of both tested cancer cell lines. All other extracts selectively inhibited SW-480 cell viability, but did not show significant cytotoxic activity. The mushroom extracts caused changes in the prooxidant/antioxidant status of cells, inducing oxidative stress. All extracts tested on HCT-116 cells demonstrated significant antimigratory effects, which correlated with increased production of O2•- and a reduced level of ß-catenin protein expression, while only P. linteus showed the same effect on SW-480 cells. The results of the present research indicate that the mushroom extracts causes oxidative stress which has a pronounced impact on the migratory status of colon cancer cell lines