Search results for "CELL SURVIVAL"
showing 10 items of 870 documents
Heme oxygenase-1 induction modulates microsomal prostaglandin E synthase-1 expression and prostaglandin E2 production in osteoarthritic chondrocytes
2009
Pro-inflammatory cytokines such as interleukin-1beta (IL-1beta) may participate in the pathogenesis of cartilage damage in osteoarthritis (OA) through the production of catabolic enzymes and inflammatory mediators. Induction of heme oxygenase-1 (HO-1) has previously been shown to exert anti-inflammatory effects in different cell types. We have investigated whether HO-1 induction may modify chondrocyte viability and the production of relevant mediators such as oxidative stress and prostaglandin E(2) (PGE(2)) elicited by IL-1beta in OA chondrocytes. Chondrocytes were isolated from OA cartilage and used in primary culture. Cells were stimulated with IL-1beta in the absence or presence of the H…
Effect of Chlorotriphenyl Derivatives of Sn and Pb upon Biophysical Properties of Membranes
2009
Biophysical activity of two twin organometallic compounds Triphenyltin chloride (TPhT) and Triphenyllead chloride (TPhL) in their interreaction with model membranes, as well as with yeast cellsSaccharomyces cerevisiae, was investigated. Four measurement methods were used in the experiments: two physical methods (spin probes method and the electric method); two biological methods (minimal inhibitory concentration /MIC/ and yeast survival test). It has been found that the activity of TPhT in interaction with model membranes and yeast cells is distinctly greater than that of TPhL. The activity manifests itself by considerable increase in the fluidity of the middle part of liposome bilayer, cha…
Synthesis and biological evaluation of papain-family cathepsin L-like cysteine protease inhibitors containing a 1,4-benzodiazepine scaffold as antipr…
2014
Novel papain-family cathepsin L-like cysteine protease inhibitors endowed with antitrypanosomal and antimalarial activity were developed, through an optimization study of previously developed inhibitors. In the present work, we studied the structure-activity relationships of these derivatives, with the aim to develop new analogues with a simplified and more synthetically accessible structure and with improved antiparasitic activity. The structure of the model compounds was significantly simplified by modifying or even eliminating the side chain appended at the C3 atom of the benzodiazepine scaffold. In addition, a simple methylene spacer of appropriate length was inserted between the benzod…
Acidic Environment Leads to ROS-Induced MAPK Signaling in Cancer Cells
2011
Tumor micromilieu often shows pronounced acidosis forcing cells to adapt their phenotype towards enhanced tumorigenesis induced by altered cellular signalling and transcriptional regulation. In the presents study mechanisms and potential consequences of the crosstalk between extra- and intracellular pH (pH(e), pH(i)) and mitogen-activated-protein-kinases (ERK1/2, p38) was analyzed. Data were obtained mainly in AT1 R-3327 prostate carcinoma cells, but the principle importance was confirmed in 5 other cell types. Extracellular acidosis leads to a rapid and sustained decrease of pH(i) in parallel to p38 phosphorylation in all cell types and to ERK1/2 phosphorylation in 3 of 6 cell types. Furth…
Heparin-binding protein targeted to mitochondrial compartments protects endothelial cells from apoptosis.
1999
Neutrophil-borne heparin-binding protein (HBP) is a multifunctional protein involved in the progression of inflammation. HBP is stored in neutrophil granules and released upon stimulation of the cells in proximity to endothelial cells. HBP affects endothelial cells in multiple ways; however, the molecular and cellular mechanisms underlying the interaction of HBP with these cells are unknown. Affinity isolation and enzymatic degradation demonstrated that HBP released from human neutrophils binds to endothelial cell-surface proteoglycans, such as syndecans and glypican. Flow cytometry indicated that a significant fraction of proteoglycan-bound HBP is taken up by the endothelial cells, and we …
Exploring the anticancer potential of pyrazolo[1,2-a]benzo[1,2,3,4] tetrazin-3-one derivatives: The effect on apoptosis induction, cell cycle and pro…
2013
In order to investigate their anticancer potential, four new pyrazolo[1,2-a]benzo[1,2,3,4]-tetrazinone derivatives, designed through the chemometric protocol VLAK, and three of the most active compounds of the previous series have been evaluated on some cellular events including proliferation, apoptosis induction, and cell cycle. The NCI one dose (10 mu M) screening revealed that the 8,9-di-methyl derivative showed activity against Leukemia (CCRF-CEM) and Colon cancer cell line (COLO 205), reaching 81% and 45% of growth inhibition (GI), respectively. Replacement of the two methyl groups with two chlorine atoms maintained the activity toward Leukemia cell (CCRF-CEM, GI 77%) and selectively e…
Inhibition by cellular vacuolar ATPase impairs human papillomavirus uncoating and infection.
2014
ABSTRACT Several viruses, including human papillomaviruses, depend on endosomal acidification for successful infection. Hence, the multisubunit enzyme vacuolar ATPase (V-ATPase), which is mainly responsible for endosome acidification in the cell, represents an attractive target for antiviral strategies. In the present study, we show that V-ATPase is required for human papillomavirus (HPV) infection and that uncoating/disassembly but not endocytosis is affected by V-ATPase inhibition. The infection inhibitory potencies of saliphenylhalamide, a proven V-ATPase inhibitor, and its derivatives, as well as those of other V-ATPase inhibitors, were analyzed on different HPV types in relevant cell l…
Computational discovery of novel trypanosomicidal drug-like chemicals by using bond-based non-stochastic and stochastic quadratic maps and linear dis…
2009
Herein we present results of a quantitative structure-activity relationship (QSAR) studies to classify and design, in a rational way, new antitrypanosomal compounds by using non-stochastic and stochastic bond-based quadratic indices. A data set of 440 organic chemicals, 143 with antitrypanosomal activity and 297 having other clinical uses, is used to develop QSAR models based on linear discriminant analysis (LDA). Non-stochastic model correctly classifies more than 93% and 95% of chemicals in both training and external prediction groups, respectively. On the other hand, the stochastic model shows an accuracy of about the 87% for both series. As an experiment of virtual lead generation, the …
Energy Metabolism Analysis of Three Different Mesenchymal Stem Cell Populations of Umbilical Cord Under Normal and Pathologic Conditions
2020
AbstractHuman umbilical cord mesenchymal stem cells (hUC-MSCs) are a pivotal source of therapeutically active cells for regenerative medicine due to their multipotent differentiation potential, immunomodulatory and anti-inflammatory proprieties, as well as logistical collection advantages without ethical concerns. However, it remains poorly understood whether MSCs from different compartments of the human umbilical cord are therapeutically superior than others. In this study, MSCs were isolated from Wharton’s jelly (WJ-MSCs), perivascular region (PV-MSCs) and cord lining (CL-MSCs) of hUC. These cells expressed the mesenchymal markers (CD90, CD73), stemness marker (OCT4), endothelial cell adh…
Structural basis for the potential antitumour activity of DNA-interacting benzo[kl]xanthene lignans
2010
The biological properties and possible pharmacological applications of benzo[kl]xanthene lignans, rare among natural products and synthetic compounds, are almost unexplored. In the present contribution, the possible interaction of six synthetic benzo[kl]xanthene lignans and the natural metabolite rufescidride with DNA has been investigated through a combined STD-NMR and molecular docking approach, paralleled by in vitro biological assays on their antiproliferative activity towards two different cancer cell lines: SW 480 and HepG2. Our data suggest that the benzo[kl]xanthene lignans are suitable lead compounds for the design of DNA selective ligands with potential antitumour properties.