Search results for "cell survival"
showing 10 items of 870 documents
Discovery of new G-quadruplex binding chemotypes
2013
We report here on the discovery and preliminary evaluation of a novel non-macrocyclic low molecular weight quadruplex-stabilizing chemotype. The lead compounds, based on a furan core, show high G-quadruplex stabilisation and selectivity as well as potent in vitro anti-proliferative activity.
A novel moniliformin derivative as pan-inhibitor of histone deacetylases triggering apoptosis of leukemia cells
2021
New and potent agents that evade multidrug resistance (MDR) and inhibit epigenetic modifications are of great interest in cancer drug development. Here, we describe that a moniliformin derivative (IUPAC name: 3-(naphthalen-2-ylsulfanyl)-4-{[(2Z)-1,3,3-trimethyl-2,3-dihydro-1H-indol-2-ylidene]methyl}cyclobut-3-ene-1,2-dione; code: MCC1381) bypasses P-gp-mediated MDR. Using transcriptomics, we identified a large number of genes significantly regulated in response to MCC1381, which affected the cell cycle and disturbed cellular death and survival. The potential targets of MCC1381 might be histone deacetylases (HDACs) as predicted by SwissTargetPrediction. In silico studies confirmed that MCC13…
Essential oils of Salvia bracteata and Salvia rubifolia from Lebanon: Chemical composition, antimicrobial activity and inhibitory effect on human mel…
2009
Aim of the study: Salvia bracteata Banks et Sol. and Salvia rubifolia Boiss. are known in folk medicine of Lebanon for the treatment of microbial infections, cancer, urinary and pulmonary problems. In the present study the chemical composition and antimicrobial activity of essential oils from aerial parts of Salvia bracteata and Salvia rubifolia collected in Lebanon were evaluated. The oils were also tested for their potential antiproliferative effects against M14 human melanoma cells. Material and methods: The oils were studied by GC and GC-MS and their antibacterial activity (MIC and MBC) was tested against ten bacteria species using the broth dilution method. The inhibitory effect on hum…
Involvement of enniatins-induced cytotoxicity in human HepG2 cells.
2012
Enniatins (ENNs) are mycotoxins found in Fusarium fungi and they appear in nature as mixtures of cyclic depsipeptides. The ability to form ionophores in the cell membrane is related to their cytotoxicity. Changes in ion distribution between inner and outer phases of the mitochondria affect to their metabolism, proton gradient, and chemiosmotic coupling, so a mitochondrial toxicity analysis of enniatins is highly recommended because they host the homeostasis required for cellular survival. Two ENNs, ENN A and ENN B on hepatocarcinoma cells (HepG2) at 1.5 and 3 μM and three exposure times (24, 48 and 72 h) were studied. Flow cytometry was used to examine their effects on cell proliferation, t…
Uridine enhances the cytotoxic effect of D-glucosamine in rat C6 glioma cells.
1986
This paper studies the influence of uridine on the effects exerted by D-glucosamine in rat C6 glioma cells. 2 mM uridine increased markedly both the cytotoxic effect of the aminosugar and the inhibition of thymidine incorporation into acid-insoluble fraction. Furthermore the complete resumption of the capacity to incorporate either 3H-thymidine or 3H-mannose which was observed after the removal of the aminosugar, was impeded when the cells were treated contemporaneously with D-glucosamine and uridine. An exposure for 4 hr to 20 mM glucosamine alone enhanced about 15-fold the cellular pool of UDP-N-acetylhexosamines; the addition of 2 mM uridine intensified the expansion of this pool, which …
Membrane protein oxidation determines neuronal degeneration
2015
Oxidative stress is an early hallmark in neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. However, the critical biochemical effector mechanisms of oxidative neurotoxicity have remained surprisingly elusive. In screening various peroxides and potential substrates of oxidation for their effect on neuronal survival, we observed that intramembrane compounds were significantly more active than aqueous or amphiphilic compounds. To better understand this result, we synthesized a series of competitive and site-specific membrane protein oxidation inhibitors termed aminoacyllipids, whose structures were designed on the basis of amino acids frequently found at the protein-lipi…
Response of Chinese Hamster V79 Multicellular Spheroids Exposed to High-Energy Carbon Ions
2004
Chinese hamster V79-379A spheroids 200 +/- 30 microm (+/- SD) in diameter were irradiated in agitated medium in different oxygen atmospheres with (1) 227 MeV/nucleon (12)C(+6) ions (plateau region) to model tissue in the entrance channel during therapy, (2) carbon ions in the extended Bragg peak modeling tissue in the target volume, or (3) X rays as a reference modality. Cell survival curves were similar for modes (1) and (3), indicating the absence of a contact effect and the presence of a pronounced oxygen effect with oxygen enhancement ratios (OERs) of 2.8 and 2.9, respectively. In contrast, the oxygen effect was substantially smaller in mode (2) with an OER of 1.4. Under normal or restr…
Galantamine modulates nicotinic receptor and blocks Aβ-enhanced glutamate toxicity
2004
Galantamine is a plant alkaloid that is used in the treatment of Alzheimer's disease. We have studied the effects of galantamine on beta-amyloid-enhanced glutamate toxicity using primary rat cultured cortical neurons. Nicotine and galantamine alone, and in combination, protected neurons against this neurotoxicity. The protection was not blocked by alpha4beta2 nicotinic acetylcholine receptor (nAChR) antagonists, but was partially blocked by alpha7 nAChR antagonists. Galantamine induced phosphorylation of Akt, an effector of phosphatidylinositol 3-kinase (PI3K), while PI3K inhibitors blocked the protective effect and Akt phosphorylation. The antibody FK1, which selectively blocks the alloste…
Induction of apoptosis by arachidonic acid in human retinoblastoma Y79 cells: involvement of oxidative stress
2000
Arachidonic acid administration caused apoptosis in Y79 cells, as shown by typical morphological changes, phosphatidylserine externalization, chromatin condensation, processing and activation of caspase-3 and cleavage of the endogenous caspase substrate poly-(ADP-ribose)-polymerase. Arachidonic acid also caused lamin B cleavage, suggesting caspase-6 activation. Arachidonic acid treatment was accompanied by increased formation of the lipid peroxidation end products malondialdehyde and 4-hydroxy-2-nonenal, lowering in reduced glutathione content and in mitochondrial membrane potential. Inhibiting glutathione synthesis sensitized Y79 cells to apoptosis-inducing stimuli, whilst replenishing red…
Hsp60 is actively secreted by human tumor cells
2010
Background Hsp60, a Group I mitochondrial chaperonin, is classically considered an intracellular chaperone with residence in the mitochondria; nonetheless, in the last few years it has been found extracellularly as well as in the cell membrane. Important questions remain pertaining to extracellular Hsp60 such as how generalized is its occurrence outside cells, what are its extracellular functions and the translocation mechanisms that transport the chaperone outside of the cell. These questions are particularly relevant for cancer biology since it is believed that extracellular chaperones, like Hsp70, may play an active role in tumor growth and dissemination. Methodology/Principal Findings S…