Search results for "G2"
showing 10 items of 439 documents
Ofd1, a Human Disease Gene, Regulates the Length and Distal Structure of Centrioles
2010
SUMMARYCentrosomes and their component centrioles represent the principal microtubule organizing centers of animal cells. Here we show that the gene underlying Orofaciodigital Syndrome 1, Ofd1, is a component of the distal centriole that controls centriole length. In the absence of Ofd1, distal regions of centrioles, but not procentrioles, elongate abnormally. These long centrioles are structurally similar to normal centrioles, but contain destabilized microtubules with abnormal post-translational modifications. Ofd1 is also important for centriole distal appendage formation and centriolar recruitment of the intraflagellar transport protein Ift88. To model OFD1 Syndrome in embryonic stem ce…
Escherichia coli cytolethal distending toxin blocks the HeLa cell cycle at the G2/M transition by preventing cdc2 protein kinase dephosphorylation an…
1997
Cytolethal distending toxins (CDT) constitute an emerging heterogeneous family of bacterial toxins whose common biological property is to inhibit the proliferation of cells in culture by blocking their cycle at G2/M phase. In this study, we investigated the molecular mechanisms underlying the block caused by CDT from Escherichia coli on synchronized HeLa cell cultures. To this end, we studied specifically the behavior of the two subunits of the complex that determines entry into mitosis, i.e., cyclin B1, the regulatory unit, and cdc2 protein kinase, the catalytic unit. We thus demonstrate that CDT causes cell accumulation in G2 and not in M, that it does not slow the progression of cells th…
The Cell Cycle-Specific Growth-Inhibitory Factor Produced by Actinobacillus actinomycetemcomitans Is a Cytolethal Distending Toxin
1998
ABSTRACT Actinobacillus actinomycetemcomitans has been shown to produce a soluble cytotoxic factor(s) distinct from leukotoxin. We have identified in A. actinomycetemcomitans Y4 a cluster of genes encoding a cytolethal distending toxin (CDT). This new member of the CDT family is similar to the CDT produced by Haemophilus ducreyi . The CDT from A. actinomycetemcomitans was produced in Escherichia coli and was able to induce cell distension, growth arrest in G 2 /M phase, nucleus swelling, and chromatin fragmentation in HeLa cells. The three proteins, CDTA, -B and -C, encoded by the cdt locus were all required for toxin activity. Antiserum raised against recombinant CDTC completely inhibited …
Apoptosis induced in hepatoblastoma HepG2 cells by the proteasome inhibitor MG132 is associated with hydrogen peroxide production, expression of Bcl-…
2002
This report is focused on the apoptotic effect induced by MG132, an inhibitor of 26S proteasome, in human hepatoma HepG2 cells. The results were compared with those obtained with non-transformed human Chang liver cells. MG132 reduced the viability of HepG2 cells in a time- and dose-dependent manner. The effect was in tight connection with the induction of apoptosis, as indicated by fluorescence microscopy and cytometric analysis, and was accompanied by a remarkable increase in the production of H2O2 and a reduction in mitochondrial transmembrane potential (Deltapsim). In addition cell death was prevented by antioxidants such as GSH, N-acetylcysteine or catalase. Western blot analysis showed…
Design, synthesis, and biological evaluation of thiophene analogues of chalcones.
2008
Chalcones are characterized by possessing an enone moiety between two aromatic rings. A series of chalcone-like agents, in which the double bond of the enone system is embedded within a thiophene ring, were synthesized and evaluated for antiproliferative activity and inhibition of tubulin assembly and colchicine binding to tubulin. The replacement of the double bond with a thiophene maintains antiproliferative activity and therefore must not significantly alter the relative conformation of the two aryl rings. The synthesized compounds were found to inhibit the growth of several cancer cell lines at nanomolar to low micromolar concentrations. In general, all compounds having significant anti…
Beauvericin-induced cytotoxicity via ROS production and mitochondrial damage in Caco-2 cells.
2013
The cytotoxicity of beauvericin (BEA) on human colon adenocarcinoma (Caco-2) cells was studied as a function of time. Moreover, the oxidative damage and cell death endpoints were monitored after 24, 48 and 72 h. After BEA exposure, the IC₅₀ values ranged from 1.9 ± 0.7 to 20.6 ± 6.9 μM. A decrease in reduced glutathione (GSH; 31%) levels, as well as an increase in oxidized glutathione (GSSG, 20%) was observed. In the presence of BEA, reactive oxygen species (ROS) level was highly increased at an early stage with the highest production of 2.0-fold higher than the control that was observed at 120 min. BEA induced cell death by mitochondria-dependent apoptotic process with loss of the mitochon…
TTAS a New Stilbene Derivative that Induces Apoptosis in Leishmania Infantum
2012
Leishmania parasites are able to undergo apoptosis (programmed cell death), similarly to mammalian cells. Recently it was demonstrated in vitro the anti-leishmanial effect of some natural and synthetic stilbenoids including resveratrol and piceatannol. In this study we evaluated the Leishmanicidal activity of a pool of stilbene derivatives which had previously shown high apoptotic efficacy against neoplastic cells. All the compounds tested were capable to decrease the parasite viability in a dose-dependent manner. Trans-stilbenes proved to be markedly more effective than cis-isomers. This was different from that observed in tumor cells in which cis-stilbenes were more potent cytotoxic agent…
Staurosporine-induced apoptosis in Chang liver cells is associated with down-regulation of Bcl-2 and Bcl-XL.
2004
A potent inhibitor of serine/threonine kinases, staurosporine exerts antiproliferative and apoptotic effects in many cancer cells, although the exact mechanism of its action is still unclear. This study examines the effects of staurosporine on Chang liver cells, an immortalized non-tumor cell line, in comparison with those caused in HuH-6 and HepG2 cells, two human hepatoma cell lines. Our results provide evidence that staurosporine promotes apoptosis in Chang liver cells as observed by flow cytometric analysis and acridine orange/ethidium bromide staining. The effect appeared already after 8 h of treatment and increased with treatment time and dose. After 48 h of exposure to 200 nM stauros…
Curcumin and trans-resveratrol exert cell cycle-dependent radioprotective or radiosensitizing effects as elucidated by the PCC and G2-assay
2013
Curcumin and trans-resveratrol are well-known antioxidant polyphenols with radiomodulatory properties, radioprotecting non-cancerous cells while radiosensitizing tumor cells. This dual action may be the result of their radical scavenging properties and their effects on cell-cycle checkpoints that are activated in response to radiation-induced chromosomal damage. It could be also caused by their effect on regulatory pathways with impact on detoxification enzymes, the up-regulation of endogenous protective systems, and cell-cycle-dependent processes of DNA damage. This work aims to elucidate the mechanisms underlying the dual action of these polyphenols and investigates under which conditions…
Type III Secretion-Dependent Cell Cycle Block Caused in HeLa Cells by Enteropathogenic Escherichia coliO103
2001
ABSTRACT Rabbit enteropathogenic Escherichia coli (EPEC) O103 induces in HeLa cells an irreversible cytopathic effect characterized by the recruitment of focal adhesions, formation of stress fibers, and inhibition of cell proliferation. We have characterized the modalities of the proliferation arrest and investigated its underlying mechanisms. We found that HeLa cells that were exposed to the rabbit EPEC O103 strain E22 progressively accumulated at 4C DNA content and did not enter mitosis. A significant proportion of the cells were able to reinitiate DNA synthesis without division, leading to 8C DNA content. This cell cycle inhibition by E22 was abrogated in mutants lacking EspA, -B, and -D…