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Autophagy is a dynamic process, conserved in all eukaryotes. It is responsible for the degradation of cytoplasmic content. Autophagy is crucial in cell survival and cell death. It plays a significant role in the cell response to stress, nutrient deficiencies, embryonic development, tumor suppression, response to pathogens and aging. The process of autophagy is also involved in the pathology of human diseases, such as cancer, diabetes, cardiomyopathy, and neurodegenerative diseases such as Alzheimer's and Parkinson's disease. Autophagy is a mechanism that involves degradation of cells, proteins, damaged organelles and pathogens through the lysosomal mechanisms, thus autophagy supports cell survival during starvation, hypoxia and metabolic stress. However, if extensive and/or excessive, autophagy can promote apoptosis (type I) or function as an alternative cell-death pathway, called autophagic cell death (type II). Autophagy can either promote cancer cell death, or serve as a survival mechanism against apoptosis or necrosis induced by various anticancer treatments. Given the contradictory role of autophagy during tumor initiation and progression, the use of autophagy in therapy depends on the context and must be approached individually

Abstract Twelve previously synthesized, biologically active 2,6,7-trihydroxyxanthen-3-one derivatives were evaluated in vitro for antiproliferative activity. Compounds were screened against HeLa, SW620, HepG2 and A549 tumor cell lines. Compound with the trifluormethyl group on C-4’ position of the phenyl ring showed the best inhibitory activity towards HeLa and A549 tumor cells with IC50 of 0.7 and 4.1 µmol L−1, resp. Compound with chlorine and fluorine substituents on aryl ring showed the best antiproliferative activity against SW620 with IC50 of 4.1 µmol L–1 and against HepG2 tumor cell line with IC50 of 4.2 µmol L–1. Analyses of cytotoxic and genotoxic potential of the trifluormethyl derivative were performed with cytokinesis-block micronucleus cytome assay in human lymphocyte culture and revealed no genotoxic and cytotoxic effects. The most potent compounds were subjected to molecular docking simulations in order to analyse bindings to molecular targets and, at the same time, further support the results of experimental cytotoxic tests. Docking studies showed sites of importance in forming hydrogen bonds of the most potent compounds with targets of interest.

Apoptosis, as a well-studied process of a programmed cell death, is essential for the maintenance of cell homeostasis and integrity of organisms. This process occurs normally during development and aging and it is a balance of the sustainability of the tissue cell population. In addition, apoptosis also occurs as a defensive mechanism such as an immune response or after cell damage as a consequence of a pathological condition or the action of harmful agents. Apoptotic activation tends to be less responsive with aging, causing accumulation of non-functional cells and pathological changes such are degenerative diseases or tumor transformation. This overview aims to provide summarized facts about different approaches of apoptosis research, targeting and regulation in tumors especially in leukemic cells as a way of pharmacological manipulation with a potential therapeutic benefit.

Inducing cell death in tumor cells has been recognized as a promising strategy in curing tumors. Parallely, natural products, especially those with long-known usage in folk medicine, are gaining demanding and extensive clinical interests. Aiming to contribute to overall knowledge of curcumin and luteolin antitumour potentials, we analyzed their effects on cell death induction in NFS-60 cell line, using Trypan blue exclusion assay and TransDetect® Anenexin V-EGFP/PI assay. Results show that both tested agents induce cell death, especially in higher applied concentrations, but further investigations are needed to elucidate the mechanisms behind it.

Micromeria pulegium (Rochel) Benth. is an endemic species of Lamiacea family that includes frequently used plants in culinary and folk medicine. As cytotoxic potential of some species of Micromeria genus has been confirmed, this study aimed to test unknown antiproliferative and genotoxic potential of M. pulegium, endemic bh species, aqueous leaf extract in normal (human lymphocytes) and cancer (human melanoma GR-M) cells in order to protect small populations of native M. pulegium populations or promote its controlled micropropagation or cultivation. Cytokinesis-block micronucleus cytome assay was applied for human lymphocyte cultures, while trypan blue exclusion assay was used for evaluation of cytotoxicity in human GR-M melanoma cells. Results demonstrate no genotoxic effects up to concentration of 0.2 mg/ml in human lymphocyte in vitro but significant reduction of cell viability in human GR-M melanoma cell line cultures treated with 0.3 mg/ml of Micromeria extract.

A. Haverić, Damira Inajetović, Aneta Vareškić, M. Hadzic, S. Haverić

Tartrazine (E 102) is widely used yellow food colorant. It is used in nonalcoholic and sports drinks, spicy chips, jams, jelly and chewing gum and also found in many non-food products like soaps, cosmetics, shampoo, vitamins and some drugs. Tartrazine belongs to the most important and diverse group of synthetic dyes – azo dyes. Their use often creates controversies in the public since some of them are toxic, carcinogenic, mutagenic and cause different disorders or allergic reactions. In this study we aimed to evaluate genotoxic potential of tartrazine in human lymphocytes culture and its cytotoxic potential in human lymphocytes and melanoma GR-M cell line. For testing of its genotoxic and cytotoxic potential in human lymphocyte culture, we used chromosome aberration analysis and cytokinesis-block micronucleus cytome assay. For the analysis of its cytotoxic potential in human melanoma cell culture, we applied trypan blue exclusion assay.

Introduction: Cigarette smoking is associated with severe health problems, especially cancers. In addition, cigarette smoking causes different genotoxic effects. Chromosome aberrations are one of well-known intermediate end points in carcinogenesis. The aim of this study was to compare frequencies of chromosome aberrations in peripheral blood lymphocytes between young smokers and non-smokes groups.Methods: The study was conducted with 30 smokers (average age 26.93 years) and 30 non-smokers (average age 26.96 years), and included the analysis of 100 metaphases per each blood sample. Differences in the arithmetic means of determined frequencies of chromosome aberrations were tested by two-tailed t-test for independent samples with the significance level of p < 0.05.Results: The results showed a significant increase in the frequencies of chromatid-type aberrations and total structural chromosome aberrations in smoker group. Frequencies of numerical aberrations did not differ significantly between two groups.Conclusions: This study confirmed genotoxicity of cigarette smoking and provided new evidence about its clastogenic activity.

Introduction: The objective of the present study was to evaluate the antimicrobial and cytotoxic activities of water extracts of leaves and barks from Alnus glutinosa (L.) Gaertn., A. incana (L.) Moench, and A. viridis (Chaix) DC.Methods: The antimicrobial activities of extracts were tested against gram-negative and gram-positive bacteria as well as yeast strains by the agar diffusion method. The cell viability was determined by the Trypan blue dye exclusion method.Results: The largest diameters of inhibition zone (DIZ) were recorded with Staphylococcus aureus ATCC 6538 and Bacillus subtilis 168M. The highest percentage of cell viability was observed with water bark extracts of A. glutinosa (97.46%).Conclusions: Potential antimicrobial properties of A. glutinosa, A. incana, and A. viridis demonstrated in this study, as well as their low levels of toxicity, make them an interesting subject for further studies.

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