Evaluation of anticancer activity of urotropine surface modified iron oxide nanoparticles using a panel of forty breast cancer cell lines.

Urotropine, an antibacterial agent to treat urinary tract bacterial infections, can be also considered as a repurposed drug with formaldehyde-mediated anticancer activity. Recently, we have synthesized urotropine surface modified iron oxide nanoparticles (URO@FeO NPs) with improved colloidal stability and limited cytotoxicity against human fibroblasts. In the present study, we have investigated URO@FeO NP-mediated responses in a panel of forty phenotypically different breast cancer cell lines along with three non-cancerous corresponding cell lines.

New Mitochondria-Targeted Fisetin Derivative Compromises Mitophagy and Limits Survival of Drug-Induced Senescent Breast Cancer Cells.

Mitochondria are considered as promising targets for cancer treatment. In the present study, triphenyl phosphonium cationic group-conjugated fisetin (mito-fisetin) was synthesized, and its anticancer activity was investigated in several cellular models of estrogen receptor (ER)-positive breast cancer in vitro and in vivo in proliferating and tamoxifen-promoted senescent states. Mito-fisetin, when used at low micromolar concentrations, stimulated the dissipation of mitochondrial membrane potential and oxidative stress, and affected mitochondrial function, resulting in apoptosis induction in senescent breast cancer cells.

Glucotoxicity is mediated by cytoplasmic distribution of RAP1 in pancreatic β-cells.

Diabetes mellitus (DM) is a group of chronic metabolic disorders characterized by persistent hyperglycemia. In our study, we analyzed the level and location of RAP1 changes in the development of β-cell dysfunction induced by glucotoxicity. We employed three pancreatic β-cell lines, namely INS-1, 1.

Mutation Status and Glucose Availability Affect the Response to Mitochondria-Targeted Quercetin Derivative in Breast Cancer Cells.

Mitochondria, the main cellular power stations, are important modulators of redox-sensitive signaling pathways that may determine cell survival and cell death decisions. As mitochondrial function is essential for tumorigenesis and cancer progression, mitochondrial targeting has been proposed as an attractive anticancer strategy. In the present study, three mitochondria-targeted quercetin derivatives (mitQ3, 5, and 7) were synthesized and tested against six breast cancer cell lines with different mutation and receptor status, namely ER-positive MCF-7, HER2-positive SK-BR-3, and four triple-negative (TNBC) cells, i.

Electrospun fiber-based micro- and nano-system for delivery of high concentrated quercetin to cancer cells.

The anticancer potential of quercetin (Q), a plant-derived flavonoid, and underlining molecular mechanisms are widely documented in cellular models in vitro. However, biomedical applications of Q are limited due to its low bioavailability and hydrophilicity. In the present study, the electrospinning approach was used to obtain polylactide (PLA) and PLA and polyethylene oxide (PEO)-based micro- and nanofibers containing Q, namely PLA/Q and PLA/PEO/Q, respectively, in a form of non-woven fabrics.

Telomere loss is accompanied by decreased pool of shelterin proteins TRF2 and RAP1, elevated levels of TERRA and enhanced glycolysis in imatinib-resistant CML cells.

Telomere length may be maintained by telomerase nucleoprotein complex and shelterin complex, namely TRF1, TRF2, TIN2, TPP1, POT1 and RAP1 proteins and modulated by TERRA expression. Telomere loss is observed during progression of chronic myeloid leukemia (CML) from the chronic phase (CML-CP) to the blastic phase (CML-BP). The introduction of tyrosine kinase inhibitors (TKIs), such as imatinib (IM), has changed outcome for majority of patients, however, a number of patients treated with TKIs may develop drug resistance.

The interplay between telomeric complex members and BCR::ABL1 oncogenic tyrosine kinase in the maintenance of telomere length in chronic myeloid leukemia.

Purpose: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by recurrent genetic aberration in leukemic stem cells, namely Philadelphia chromosome caused by reciprocal translocation t(9;22)(q34;q11). In our study, we analyzed the telomeric complex expression and function in the molecular pathogenesis of CML.

Methods: We employed CD34+ primary leukemic cells, comprising both leukemic stem and progenitor cell populations, isolated from peripheral blood or bone marrow of CML patients in chronic and blastic phase to analyze the telomere length and telomeric-associated proteins.

RAP1/TERF2IP-A Multifunctional Player in Cancer Development.

Mammalian RAP1 (TERF2IP), the most conserved shelterin component, plays a pleiotropic role in the regulation of a variety of cellular processes, including cell metabolism, DNA damage response, and NF-κB signaling, beyond its canonical telomeric role. Moreover, it has been demonstrated to be involved in oncogenesis, progression, and chemoresistance in human cancers. Several mutations and different expression patterns of RAP1 in cancers have been reported.

The Identification of a Novel Fucosidosis-Associated Mutation: A Case of a 5-Year-Old Polish Girl with Two Additional Rare Chromosomal Aberrations and Affected DNA Methylation Patterns.

Fucosidosis is a rare neurodegenerative autosomal recessive disorder, which manifests as progressive neurological and psychomotor deterioration, growth retardation, skin and skeletal abnormalities, intellectual disability and coarsening of facial features. It is caused by biallelic mutations in encoding the α-L-fucosidase enzyme, which in turn is responsible for degradation of fucose-containing glycoproteins and glycolipids. mutations lead to severe reduction or even loss of α-L-fucosidase enzyme activity.

Differential Regulation of Telomeric Complex by Kinase in Human Cellular Models of Chronic Myeloid Leukemia-From Single Cell Analysis to Next-Generation Sequencing.

Telomeres are specialized nucleoprotein complexes, localized at the physical ends of chromosomes, that contribute to the maintenance of genome stability. One of the features of chronic myeloid leukemia (CML) cells is a reduction in telomere length which may result in increased genomic instability and progression of the disease. Aberrant telomere maintenance in CML is not fully understood and other mechanisms such as the alternative lengthening of telomeres (ALT) are involved.

In vitro exposure to thiacloprid-based insecticide formulation promotes oxidative stress, apoptosis and genetic instability in bovine lymphocytes.

A proprietary thiacloprid-based neonicotinoid insecticide formulation is widely used in agriculture to protect vegetables and fruit against various pests. However, its effect on animal cells has not been fully elucidated. In this study, bovine peripheral lymphocytes were incubated with different concentrations of this formulation (10; 30; 60; 120 and 240 μg.

c-Myc activation promotes cofilin-mediated F-actin cytoskeleton remodeling and telomere homeostasis as a response to oxidant-based DNA damage in medulloblastoma cells.

Medulloblastoma (MB) is a common and highly aggressive pediatric brain tumor of a heterogeneous nature. According to transcriptome-based profiling, four molecular subgroups of MB have been revealed, namely WNT, SHH, Group 3 and Group 4. High MYC mRNA expression and MYC gene amplification in MB have been considered as indicators of poor prognosis.

Sulforaphane-Induced Cell Cycle Arrest and Senescence are accompanied by DNA Hypomethylation and Changes in microRNA Profile in Breast Cancer Cells.

Cancer cells are characterized by genetic and epigenetic alterations and phytochemicals, epigenetic modulators, are considered as promising candidates for epigenetic therapy of cancer. In the present study, we have investigated cancer cell fates upon stimulation of breast cancer cells (MCF-7, MDA-MB-231, SK-BR-3) with low doses of sulforaphane (SFN), an isothiocyanate. SFN (5-10 µM) promoted cell cycle arrest, elevation in the levels of p21 and p27 and cellular senescence, whereas at the concentration of 20 µM, apoptosis was induced.

Reduced levels of methyltransferase DNMT2 sensitize human fibroblasts to oxidative stress and DNA damage that is accompanied by changes in proliferation-related miRNA expression.

Methyltransferase DNMT2 is suggested to be involved in the regulation of numerous processes, however its biological significance and underlying molecular mechanisms remain elusive. In the present study, we have used WI-38 and BJ human fibroblasts as an in vitro model system to investigate the effects of siRNA-based DNMT2 silencing. DNMT2-depleted cells were found to be sensitive to oxidative stress conditions as judged by increased production of reactive oxygen species and susceptible to DNA damage that resulted in the inhibition of cell proliferation.

Ursolic acid-mediated changes in glycolytic pathway promote cytotoxic autophagy and apoptosis in phenotypically different breast cancer cells.

Plant-derived pentacyclic triterpenotids with multiple biological activities are considered as promising candidates for cancer therapy and prevention. However, their mechanisms of action are not fully understood. In the present study, we have analyzed the effects of low dose treatment (5-20 µM) of ursolic acid (UA) and betulinic acid (BA) on breast cancer cells of different receptor status, namely MCF-7 (ER, PR, HER2), MDA-MB-231 (ER, PR, HER2) and SK-BR-3 (ER, PR, HER2).

Diosmin-induced senescence, apoptosis and autophagy in breast cancer cells of different p53 status and ERK activity.

Relatively low bioavailability of plant-derived nutraceuticals with anticancer properties may limit their usefulness for prevention and therapy of cancer. In the present study, we have screened for nutraceuticals (n=30) that would act at low micromolar range against phenotypically distinct breast cancer cell lines, namely MCF-7 (ER, PR, HER2), MDA-MB-231 (ER, PR, HER2) and SK-BR-3 (ER, PR, HER2), and diosmin, a citrus fruit flavonoid belonging to a flavone subclass, was selected. MCF-7 cell line was found to be the most sensitive to diosmin treatment.

Relationships between rDNA, Nop1 and Sir complex in biotechnologically relevant distillery yeasts.

Distillery yeasts are poorly characterized physiological group among the Saccharomyces sensu stricto complex. As industrial yeasts are under constant environmental stress during fermentation processes and the nucleolus is a stress sensor, in the present study, nucleolus-related parameters were evaluated in 22 commercially available distillery yeast strains. Distillery yeasts were found to be a heterogeneous group with a variable content and length of rDNA and degree of nucleolus fragmentation.

Copy number variations of genes involved in stress responses reflect the redox state and DNA damage in brewing yeasts.

The yeast strains of the Saccharomyces sensu stricto complex involved in beer production are a heterogeneous group whose genetic and genomic features are not adequately determined. Thus, the aim of the present study was to provide a genetic characterization of selected group of commercially available brewing yeasts both ale top-fermenting and lager bottom-fermenting strains. Molecular karyotyping revealed that the diversity of chromosome patterns and four strains with the most accented genetic variabilities were selected and subjected to genome-wide array-based comparative genomic hybridization (array-CGH) analysis.

Adaptive response to chronic mild ethanol stress involves ROS, sirtuins and changes in chromosome dosage in wine yeasts.

Industrial yeast strains of economic importance used in winemaking and beer production are genomically diverse and subjected to harsh environmental conditions during fermentation. In the present study, we investigated wine yeast adaptation to chronic mild alcohol stress when cells were cultured for 100 generations in the presence of non-cytotoxic ethanol concentration. Ethanol-induced reactive oxygen species (ROS) and superoxide signals promoted growth rate during passages that was accompanied by increased expression of sirtuin proteins, Sir1, Sir2 and Sir3, and DNA-binding transcription regulator Rap1.

Affected chromosome homeostasis and genomic instability of clonal yeast cultures.

Yeast cells originating from one single colony are considered genotypically and phenotypically identical. However, taking into account the cellular heterogeneity, it seems also important to monitor cell-to-cell variations within a clone population. In the present study, a comprehensive yeast karyotype screening was conducted using single chromosome comet assay.

Genome-wide array-CGH analysis reveals YRF1 gene copy number variation that modulates genetic stability in distillery yeasts.

Industrial yeasts, economically important microorganisms, are widely used in diverse biotechnological processes including brewing, winemaking and distilling. In contrast to a well-established genome of brewer's and wine yeast strains, the comprehensive evaluation of genomic features of distillery strains is lacking. In the present study, twenty two distillery yeast strains were subjected to electrophoretic karyotyping and array-based comparative genomic hybridization (array-CGH).

Genetic profiling of yeast industrial strains using in situ comparative genomic hybridization (CGH).

The genetic differences and changes in genomic stability may affect fermentation processes involving baker's, brewer's and wine yeast strains. Thus, it seems worthwhile to monitor the changes in genomic DNA copy number of industrial strains. In the present study, we developed an in situ comparative genomic hybridization (CGH) to investigate the ploidy and genetic differences between selected industrial yeast strains.

Single-cell analysis of aneuploidy events using yeast whole chromosome painting probes (WCPPs).

Aneuploidy is considered a widespread genetic variation in such cell populations as yeast strains, cell lines and cancer cells, and spontaneous changes in the chromosomal copy number may have implications for data interpretation. Thus, aneuploidy monitoring is essential during routine laboratory practice, especially while conducting biochemical and/or gene expression analyses. In the present study, we constructed a panel of whole chromosome painting probes (WCPPs) to monitor aneuploidy in a single yeast Saccharomyces cerevisiae cell.