Test corpus 2 of BioIE

[ biopathway.org | BioIE ]

Test corpus 2

One of the explanations is based on biological activation of such carcinogens by cytochromes that are also known for metabolism of caffeine.
Combining topotecan with anti-VEGF antibody significantly inhibited rebound tumor growth in comparison with anti-VEGF antibody alone.
Selective inhibition of the activities of both eukaryotic DNA polymerases and DNA topoisomerases by elenic acid.
In contrast, a general caspase inhibitor decreased camptothecin-induced cell death, but did not significantly decrease the increases in tau phosphorylation.
Inhibition of this enzyme by drugs such as topotecan and irinotecan leads to cell death and is the basis for their anticancer activity.
Antineoplastic bis(dioxopiperazine)s, such as meso-2,3-bis(2,6-dioxopiperazin-4-yl)butane (ICRF-193), are widely believed to be only catalytic inhibitors of topoisomerase II.
At the first detection of MLL-ENL, the only topoisomerase II inhibitors the patient had received were one dose of daunorubicin and two doses of etoposide.
From this observation we propose that inhibition of NO biosynthesis by CPT may underlie, at least in part, the efficacy of this antitumor agent.
A novel inhibitor of topoisomerase I designated as isoaurostatin (1) was isolated from the culture filtrate of Thermomonospora alba strain No. 1520.
The complexes decrease the re-ligation rate, disrupt the cleavage-re-ligation equilibrium, and have a net effect of increasing cleavage.
Triple-treatment with systemic dexrazoxane was superior to single dosage and completely prevented lesions after s.c. daunorubicin and doxorubicin.
The present study explored the consequences of procaspase-2S overexpression in U937 human leukemic cells exposed to the topoisomerase II inhibitor etoposide as an apoptotic stimulus.
These results suggested that activation or exposure of sialidase on the cell surface was induced by etoposide treatment and was the main cause of the decrease in sialic acids.
although these inhibitors at 10 microM concentration completely blocked caspase-3 activity, they had no effect on either the rate of cell death or on any other apoptotic features, e.g., chromatin condensation, DNA fragmentation, protein cleavage, suggesting that caspase-3 was not required to mediate nuclear destruction in these hepatoma cells.
In this study, we showed that bisdioxopiperazines induced erythroid differentiation, inhibited human leukemia K562 cell growth, and caused a slow induction of apoptosis.
Ternary complex formation results in inhibition of DNA replication and generation of permanent double-strand breaks.
In contrast, NU1025 did not increase the DNA strand breakage or cytotoxicity caused by the topoisomerase II inhibitor etoposide.
Exposure of exponentially growing gastric AGS cancer cells to CPT induced time-dependent apoptosis and growth inhibition.
However, we have previously shown that amsacrine and, to a lesser extent, doxorubicin, could induce apoptosis in the doxorubicin-resistant variant of this cell line.
growth factor/receptor-specific inhibitors (e.g., anti-GRP monoclonal antibodies, bradykinin antagonist dimers); and a variety of selective protein kinase inhibitors.
We investigated whether inhibition of telomerase activity through a hammerhead ribozyme targeting the RNA template of telomerase influences the susceptibility of human melanoma cells to a variety of anticancer agents (platinum compounds, taxanes, topoisomerase I inhibitors).
dFdG can be activated by dCK and deoxyguanosine kinase (dGK), but the latter enzyme was not altered in AG6000 cells.
When DNA topoisomerase II (topo II) activity is inhibited with a non-DNA-damaging topo II inhibitor (ICRF-193), mammalian cells become checkpoint arrested in G2-phase.
When DNA topoisomerase II (topo II) activity is inhibited with a non-DNA-damaging topo II inhibitor (ICRF-193), mammalian cells become checkpoint arrested in G2-phase.
Topo IV activity was sufficient to prevent accumulation of (+) supercoils in plasmid DNA in vivo, suggesting that topo IV can promote replication by removing (+) supercoils in front of the chromosomal fork.
Epolactaene and its derivatives selectively inhibited the activities of mammalian DNA polymerase alpha and beta and human DNA topoisomerase II, with IC(50) values of 25, 94, and 10 microM, respectively.
We have now investigated the mechanism of action of acetyl-BA and show that these compounds are more potent inhibitors of human topoisomerases I and IIalpha than camptothecin, and amsacrine or etoposide, respectively.
Increases in both the synthesis and degradation of Topo I were previously shown to accompany phytohemagglutinin stimulation of proliferation in human peripheral T lymphocytes.
Genistein induces apoptosis and topoisomerase II-mediated DNA breakage in colon cancer cells.
The topoisomerase inhibitors camptothecin and etoposide induce a CD95-independent apoptosis of activated peripheral lymphocytes.
The topoisomerase inhibitors camptothecin and etoposide induce a CD95-independent apoptosis of activated peripheral lymphocytes.
These quinolones stimulated enzyme-mediated DNA scission to a similar extent, but their potencies varied significantly.
Incubating pyF111 cells with the much slower acting, apoptogenic topoisomerase-II inhibitors etoposide (VP-16) and teniposide (VM-26) also caused within 6 h a doubling of the CP-bound holo-PKC-delta-related activity but with no significant translocation of the holoenzyme to the CP fraction.
The results showed that topoisomerase inhibitors, which were shown to be potent PCD inducers in the HL60 cell line, induced a weaker apoptotic response in SHE cells than after growth factor deprivation.
Exposure of (a) late differentiating spermatogonia (and, possibly, preleptotene spermatocytes) results in cell death; (b) early- to mid-pachytene induces specific-locus deletions and crossover reduction; and, (c) late pachytene-through-diakinesis leads to genetically unbalanced conceptuses as a result of clastogenic damage.
Hsp27 overexpression inhibits doxorubicin-induced apoptosis in human breast cancer cells.
Macrostatin inhibited topoisomerase I and II in a noncompetitive manner with Ki = 3.7 and 1.3 nM respectively.
To determine if Hoechst 33342 or Hoechst 33258 induces apoptosis in human promyelocytic leukemia cells (HL-60) and inhibits topoisomerase I activity.
Induction of apoptosis by dexrazoxane (ICRF-187) through caspases in the absence of c-jun expression and c-Jun NH2-terminal kinase 1 (JNK1) activation in VM-26-resistant CEM cells.
Anti-cancer drugs induce cellular DNA damage and cytotoxic events, leading to apoptotic cell death.
Both etoposide and m-AMSA induced more DNA cleavage with purified R162Q enzyme than with the wt.
The cellular consequences of the inhibition of topoisomerase II by cryptolepine were investigated using the HL60 leukemia cell line.
Inhibition of topoisomerase II alpha subunit de novo synthesis by specific antisense oligonucleotides suppresses human glioma T98G cell growth.
Therefore, apoptotic agents with different mechanisms of action induced the formation of large genomic DNA fragments and very similar ultrastructural changes.
6-N-formylamino-12,13-dihydro-1, 11-dihydroxy-13-(beta-D-glucopyranosil)5H-indolo [2,3-a]pyrrolo [3, 4-c]carbazole-5,7(6H)-dione (NB-506), a potent inhibitor of DNA topoisomerase I, is currently under development for the treatment of cancer.
Inhibition of cellular progression and proliferation by thiols can therefore be mediated by diverse mechanisms which include both cycle-phase specific (i.e .
Amrubicin and its C-13 alcohol metabolite, amrubicinol, inhibited purified human DNA topoisomerase II (topo II).
Compared with doxorubicin (DXR), amrubicin and amrubicinol induced extensive DNA-protein complex formation and double-strand DNA breaks in CCRF-CEM cells and KU-2 cells.
Camptothecin, but not beta-lapachone, induced accumulation of p53 and the major growth arrest-associated p53 response protein, p21.
Topoisomerase I from calf thymus gland was inhibited by delta 12,14-PGJ2, delta 12-PGJ2, and PGA2, but not inhibited by other prostaglandins even at high concentrations.
They showed excellent inhibitory effects on several tumor cell lines with nanomolar IC50 values.
Since apoptosis was only selectively induced by some of the CCS agents, it implies c-myc expression is associated with growth regulation and c-myc down-regulation is an insufficient condition for the induction of apoptosis.
Integration of the human immunodeficiency virus type 1 (HIV-1) cDNA is a required step for viral replication.
Synthesis, DNA binding, topoisomerase II inhibition and cytotoxicity of two guanidine-containing anthracene-9,10-diones.
Heliquinomycin inhibited both DNA and RNA synthesis in cell culture but did not inhibit protein synthesis.
In addition, amsacrine induced apoptosis only in the resistant line while doxorubicin did not induce apoptosis in any cell line.
No correlation was observed between the inhibitory activities of quinolones against bacterial type II topoisomerases and those against human topoisomerase II.
Taken together, these results suggest that Bcl-xL is a primary checkpoint that can block or delay transmission of cell death signals emerging from DNA damage and prevents activation of an apoptogenic proteolytic cascade.
CJ-12,373 inhibits both DNA gyrase-mediated supercoiling and relaxation without the formation of a cleavage intermediate, suggesting that CJ-12,373 inhibits DNA gyrase at a stage distinct from the religation step.
Topotecan, a camptothecin analogue, is a specific inhibitor of topoisomerase I approved for use in the treatment of patients with refractory ovarian carcinoma.
In contrast with these observations, in in vivo experiments, S16020-2 was able to induce topoisomerase II-mediated DNA strand breaks at concentrations 500-fold lower than NMHE.
The anthracyclines have been shown to intercalate with DNA and indirectly inhibit the activity of the enzyme topoisomerase II, resulting in DNA strand breaks.
Detection of topoisomerase II cleavages was strongly dependent upon one specific topoisomerase II poison, etoposide (VP-16).
The findings that mycoplasma topo is inhibited by both eukaryotic topo II and topo I antagonists and that m-AMSA and camptothecin inhibited the growth of M.
The protease inhibitor N-benzyloxycabonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD.fmk) completely prevents the activation of DEVDase and PARP cleavage, as well as the manifestation of nuclear apoptosis (chromatin condensation, DNA fragmentation, hypoploidy).
The protease inhibitor N-benzyloxycabonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD.fmk) completely prevents the activation of DEVDase and PARP cleavage, as well as the manifestation of nuclear apoptosis (chromatin condensation, DNA fragmentation, hypoploidy).
Interaction of the DNA topoisomerase II catalytic inhibitor meso-2,3-bis(3,5-dioxopiperazine-1-yl)butane (ICRF-193), a bisdioxopiperazine derivative, with the conserved region(s) of eukaryotic but not prokaryotic enzyme.
Topoisomerase I inhibitory activity of DX-8951 was about three-fold stronger than that of SN-38, as measured in crude nuclear extract obtained from SUIT-2 cells.
Inhibition of topoisomerase II by liriodenine.
More potent inhibitors of thymidylate synthase (TS) such as tomudex and trimetrexate have been developed and are currently being evaluated in the clinic either alone or in combination with 5-FU.
The quinoline analogues showed cytotoxicities broadly similar to those of the known tricyclic acridine-4-carboxamide mixed topoI/II inhibitor DACA, with thieno and indeno analogues being the most active.
Recent studies, which demonstrated that several forms of spontaneous DNA damage stimulate cleavage mediated by Drosophila topoisomerase II, suggest that DNA lesions may act as these endogenous poisons.
Topoisomerase II inhibitors induce DNA double-strand breaks at a specific site within the AML1 locus.
Previous studies have demonstrated that G1/S cell cycle blockers and inhibitors of cyclin-dependent kinases (CDKs) prevent the death of nerve growth factor (NGF)-deprived PC12 cells and sympathetic neurons, suggesting that proteins normally involved in the cell cycle may also serve to regulate neuronal apoptosis.
a glucocorticoid analog dexamethasone, an inhibitor of topoisomerase II teniposide VM26, and gamma radiation.
The depletion of spermine blocked DNA synthesis with a consequent accumulation of cells in the G1 phase of the cell cycle.
The Ca2+ activated DNA fragmentation was significantly prevented by the presence of etoposide, genistein and amsacrine with the concentrations of 10(-5) and 10(-4) M in the reaction mixture, although ATA (10(-5) and 10(-4) M) had no effect.
Fas activation of p38 correlated temporally with the onset of apoptosis, and transfection of constitutively active MKK3 (glu), an upstream regulator of p38, potentiated Fas-induced cell death, suggesting a potential involvement of the MKK3/p38 activation pathway in Fas-mediated apoptosis.
The obtained results demonstrated that the drug only inhibited the ligation reaction leaving the cleavage reaction unaffected at the studied site.
Here we demonstrate the drug induction of tetraploid cells at mitosis by interference with cell cycle checkpoints and the coordination of mitotic events.
DNA strand cleavage is required for replication fork arrest by a frozen topoisomerase-quinolone-DNA ternary complex.
These data suggest that NU/ICRF 500, 505, and 506 induce cell death, at least partly, through topo inhibition.
In contrast, when the cells were treated with high concentrations of ICRF-193 and VP-16 for 1 hour, the VP-16-induced cytotoxicity was prevented by ICRF-193 and the degree of prevention was increased by the pretreatment of cells with ICRF-193, while post-treatment with ICRF-193 had little effect on the cytotoxicity of VP-16.
Aphidicolin (inhibitor of DNA polymerases alpha and delta) applied concomitantly with CPT in cells not pretreated with BZ prevented the increase in DNA damage in LY-R cells, but was without effect in LY-S cells.
We have previously reported that phenolic moieties in compounds such as flavones, caffeic acid phenethyl ester (CAPE), tyrphostins, and curcumin confer inhibitory activity against HIV-1 integrase.
Selective inhibition of topoisomerase II by ICRF-193 does not support a role for topoisomerase II activity in the fragmentation of chromatin during apoptosis of human leukemia cells.
Both compounds have unique mechanisms of antitumor activity; CPT uniquely inhibits an enzyme, topoisomerase I, involved in DNA replication, while taxol binds to a protein, tubulin, thus inhibiting cell division.
The nature of inhibition of DNA gyrase by the coumarins and the cyclothialidines revealed by X-ray crystallography.
Etoposide (0.3-10 microM) dose-dependently inhibited proliferation and alkaline phosphatase activity.
Similarly, we found that 0.05 microM camptothecin inhibited MRC-associated topoisomerase I activity by approximately 50%.
Our results indicate that AML1 can activate the promoter, and that the chimeric proteins compete with the normal AML1 and repress expression from the CSF1R promoter.
Important areas of future research are discussed that may ultimately potentiate the efficacy and decrease the toxicity of RIT and help determine how to optimally combine RIT with other therapeutic modalities.
Azatoxin (NSC 640737), a synthetic molecule, was rationally designed as a topoisomerase-II inhibitor and was shown to be a potent cytotoxic agent that inhibits both tubulin and topoisomerase II.
Furthermore, both sensitive MCF7/WT and mitoxantrone-resistant MCF7/MX cells contain equal amounts of DNA topoisomerase I protein, and DNA relaxation activities were equal in both cell lines and inhibited to the same extent by topotecan and camptothecin.
TAN-1518 A, unlike CPT, did not stimulate Topo I-induced DNA cleavage; instead, it inhibited CPT-induced cleavable complex formation.
In contrast, DC-3F/SU 1000 cells are about 2-fold resistant to classical DNA topoisomerase II inhibitors such as doxorubicin, amsacrine, and etoposide, whereas the cells are 1.5-fold more sensitive to the topoisomerase I inhibitor camptothecin.
Inhibitors of topoisomerase II delay progress through mitosis and induce a doubling of the DNA content in CHO cells.
CP-115,953 stimulates DNA cleavage mediated by topoisomerase II with a potency approximately 600 times greater than that of ciprofloxacin, a quinolone antibacterial agent that currently is in clinical use.
Analysis of the cellular DNA content revealed that CPT induced specific changes in cell cycle distribution.
Ellagic acid and 12 related agents have been tested for their ability to inhibit the activities of human DNA topoisomerase (topo) I and II.
This enzyme is ATP and Mg2+ dependent and can relax both negatively and positively supercoiled DNA, but presents no supercoiling activity.
These results imply that topoisomerase IV could be a target for the quinolones in intact bacteria and that quinolones could inhibit not only supercoiling of DNA gyrase but also decatenation of topoisomerase IV when high concentrations of drug exist in bacterial cells.
Recovery of Topo I activities in X-irradiated hamster cells required 12 h, whereas irradiated human cells recovered in only 70 min.
Selected dicationic-substituted bis-benzimidazoles also strongly inhibited the induction of the topoisomerase I- and II-mediated cleavable complex, suggesting that the biologically active DNA minor groove-binding molecules inhibit the enzyme-DNA binding step of the topoisomerase reaction sequence.
CAPE, however, inhibited reactions 1 and 3 effectively when preincubated with the enzyme, suggesting that this compound differs from the flavones primarily in requiring more time to block the enzyme.
Inhibition of potentially lethal and sublethal damage repair by camptothecin and etoposide in human melanoma cell lines.
Representative compounds were shown to be potent inhibitors of the DNA strand-passing activity of human topoisomerase II and of the DNA decatenation activity of the corresponding parasite enzyme.
Cleavable complex formation of Topo I by camptothecin (Cpt) did not correlate with Topo I catalytic activity, while Topo I catalytic activity could equally and completely be inhibited by Cpt.
We examined the ability of these tricyclic carboxamides to induce DNA lesions that reflect the stabilization of topoisomerase II cleavage complexes.
Changes in nuclear chromatin precede internucleosomal DNA cleavage in the induction of apoptosis by etoposide.
The results of mutational analyses of yeast and human DNA topoisomerase I are presented, as well as a genetic screen designed to identify genes, other than TOP1, that are required for the cytotoxic activity of camptothecin.
In vivo inhibition of etoposide-mediated apoptosis, toxicity, and antitumor effect by the topoisomerase II-uncoupling anthracycline aclarubicin.
Irs2 showed moderate hypersensitivity (2-3-fold) to simple alkylating agents and oxidative mutagens but was most sensitive (8-fold) to the topisomerase I inhibitor camptothecin.
it absolutely requires Mg2+ for activity, relaxes negatively but not positively supercoiled DNA and is inhibited by single-stranded M13 DNA and spermidine.
These results may suggest that even though modulation of these signaling pathways was unable to prevent topoisomerase inhibitor-induced apoptosis, their sole deregulations could induce apoptosis in HL-60 cells.
These drugs induce differentiation in concentrations 10-100-fold below the lethal dose, the concentration must be sufficient to inhibit topoisomerase II but well below the concentration to induce the cleavable complex.
Woodfruticosin (woodfordin C) (WFC), a new inhibitor of DNA topoisomerase II (topo-II), was isolated from methanol extract of Woodfordia fruticosa Kurz (Lythraceae) and studied for in vitro and in vivo antitumor activities in comparison with Adriamycin (ADR) and etoposide (ETP), well known inhibitors of topo-II.
The mitochondrial activity was dependent on the presence of Mg2+ ions and could be inhibited by novobiocin and N-ethylmaleimide.
A series of ortho-quinone analogues 1-28 of podophyllotoxin possessing various C-4 beta-aniline moieties have been synthesized and evaluated for their inhibitory activity against human DNA topoisomerase II, their activity in causing cellular protein-linked DNA breakage, and their cytotoxicity against KB cells.
Nonetheless, these agents may induce prophage by producing essentially the same type of DNA damage, i.e., DNA strand breaks.
Following recovery from a 4-hr exposure to clinically achievable concentrations of the topoisomerase II inhibitors Adriamycin, teniposide, or amsacrine or the putative topoisomerase II inhibitor crisnatol, murine erythroleukemic cells remained viable for up to 48 hr, but did not proliferate.
Inhibition of topoisomerase II by antitumor agents bis(2,6-dioxopiperazine) derivatives.
BE-13793C showed strong inhibitory activity against topoisomerases I and II and inhibited the growth of doxorubicin-resistant or vincristine-resistant P388 murine leukemia cell lines, as well as their parent P388 cell line.
We investigated m-AMSA or doxorubicin (Dx) induced DNA single-strand breaks (DNA-SSB) in myeloid leukemia cells obtained from 8 adult patients suffering from AML.
The topoisomerase II inhibitors VM-26 and VP-16, which stabilize covalent DNA-topoisomerase intermediates, greatly enhance TNF cytotoxicity against both cell lines.
Activation of internucleosomal DNA cleavage in human CEM lymphocytes by glucocorticoid and novobiocin.
Bacterial topoisomerase II inhibitors (ofloxacin and its commercial derivative Tarivid, nalidixic acid, and novobiocin) were tested as blockers of Trypanosoma cruzi differentiation and proliferation.
Our results suggest that aclarubicin inhibits topoisomerase II-mediated DNA cleavage.
We propose that one reason for the rescue from mAMSA killing of at least S-phase cells by novo or 2,4-dinitrophenol is their ability transiently to inhibit replicative DNA synthesis.
Compared to (20S)-camptothecin (1a) or (20RS)-camptothecin (1b), the ring E modified analogues 2d-f display little or no cytotoxic activity, greatly reduced effect on the inhibition of topoisomerase I, and total loss of life prolongation in the in vivo L-1210 mouse leukemia assay, indicative of the highly restricted structural and electronic requirements of ring E for biological activity in camptothecin.
Acidic phospholipids inhibited the DNA relaxation activity of topoisomerase I whereas neutral phospholipid, phosphatidylethanolamine, did not.
Using trypan blue dye exclusion and colony formation, doses of HCPT ranging from 0.01 to 1 microM progressively inhibited growth in both cell lines in a concentration-dependent manner.
Treatment of infected cells with either drug prevented efficient replication of adenovirus DNA.
A good correlation was found between the degree of DNA synthesis inhibition by aphidicolin and the reduction of camptothecin cytotoxicity.
Similar selectivity for p170 was seen for teniposide-stimulated DNA cleavage or its inhibition by merbarone.
To investigate the effect of nalidixic acid on DNA repair in cultured rat hepatocytes, DNA damage was induced by ultraviolet light or N-methyl-N-nitro-N'-nitrosoguanidine.
Though earlier results suggest that RNA synthesis is an exploitable target for Q-cell cytotoxic agents, the RNA synthesis inhibitor NSC 366140 did not inhibit RNA synthesis in Q-cells.
Although novobiocin is known to inhibit DNA topoisomerase II, VM-26, a specific inhibitor of this enzyme had no effect on the transcription.
These effects are most likely directly related to the topoisomerase inhibitory effect of these drugs since topoisomerase II is involved in the separation of intertwined chromosomal DNA molecules during mitosis as well as being a mediator of DNA exchanges.
The enzymatic activity requires Mg2+ and K+.
Novobiocin inhibits DNA topoisomerases.
The type II enzyme also requires ATP or dATP; the nonhydrolyzable ATP analogues adenylyl imidodiphosphate and adenylyl (beta,gamma-methylene)diphosphonate are potent inhibitors.
Conversely, inhibition of unscheduled DNA synthesis by novobiocin is paralleled by inhibition of excision of the lesion.
Inhibitors of RNA synthesis, actinomycin D and aminonucleoside of puromycin, potentiate rather than [[inhibit]] nATPase reaction.