NK314 is a novel synthetic benzo[c]phenanthridine alkaloid that shows strong antitumor activity. It inhibited topoisomerase II activity and stabilized topoisomerase II-DNA cleavable complexes. The DNA breaks occurred within 1h after treatment with NK314 even without digestion of topoisomerase II by proteinase K, whereas etoposide required digestion of the enzyme protein in cleavable complex to detect DNA breaks. Pretreatment with topoisomerase II catalytic inhibitors, ICRF-193 and suramin, reduced both cleavable complex-mediated DNA breaks and proteinase K-independent DNA breaks, but protease inhibitors and nuclease inhibitors only decreased the latter.
TY - JOUR. T1 - Topoisomerase IIα controls the decatenation checkpoint. AU - Luo, Kuntian. AU - Yuan, Jian. AU - Chen, Junjie. AU - Lou, Zhenkun. PY - 2009. Y1 - 2009. N2 - Topoisomerase II (Topo II) is required to separate intertwined sister chromatids before chromosome segregation can occur in mitosis. However, it remains to be resolved whether Topo II has any role in checkpoint control. Here we report that when phosphorylated, Ser 1524 of Topo IIα acts as a binding site for the BRCT domain of MDC1 (mediator of DNA damage checkpoint protein-1), thereby recruiting MDC1 to chromatin. Although Topo IIα-MDC1 interaction is not required for checkpoint activation induced by DNA damage, it is required for activation of the decatenation checkpoint. Mutation of Ser 1524 results in a defective decatenation checkpoint. These results reveal an important role of Topo II in checkpoint activation and in the maintenance of genomic stability.. AB - Topoisomerase II (Topo II) is required to separate ...
A small structure-focused library of propargylic enol ethers was prepared by means of a modular and efficient chemodifferentiating organocatalyzed multicomponent reaction. The most active compound (GI50 0.25 μM) against solid tumor cells was selected as lead. Cell cycle analysis and immunoblotting demonstrated arrest at the metaphase, pointing out human topoisomerase II as plausible molecular target. In vitro assays were carried out, showing that the lead behaves as a catalytic inhibitor of the enzyme ...
Abstract. Filamin-A, also called Actin Binding Protein-280, is not only an essential component of the cytoskeleton networks, but also serves as the scaffold in various signaling networks. It has been shown that filamin-A facilitates DNA repair and filamin-A proficient cells are more resistant to ionizing radiation, bleomycin, and cisplatin. In this study, we assessed the role of filamin-A in modulating cancer cell sensitivity to Topo II poisons, including etoposide and doxorubicin. Intriguingly, we found that cells with filamin-A expression are more sensitive to Topo II poisons than those with defective filamin-A, and filamin-A proficient xenograft melanomas have better response to etoposide treatment than the filamin-A deficient tumors. This is associated with more potent induction of DNA double strand breaks (DSBs) by Topo II poisons in filamin-A proficient cells than the deficient cells. Although the expression of filamin-A enables cells a slightly stronger capability to repair DSB, the net ...
Tumors developed in BRCA1 mutation carriers show distinctive cytologic and molecular profiles compared with the sporadic tumor counterparts (1, 24). Nevertheless, at the moment, tailored treatments for this group of patients have only been partially investigated (12, 13). The rarity of human BRCA1-mutated cancer cell lines has further limited the exploitation of such approaches.. In the current study, we used the RNA interference technology to generate several isogenic BRCA1-silenced/nonsilenced breast cancer cell lines to assess whether a biological rational exists to implement therapeutic protocols specific for BRCA1 cancer patients. Our cell models were then challenged with several chemotherapeutics commonly used in breast cancer treatment.. We found no association between BRCA1 down-regulation and sensitivity to the topoisomerase II inhibitors etoposide and doxorubicin. Although differential response was observed in a few clones, this was not correlated to BRCA1 expression levels. ...
A 990581 was a 2-pyridone novel DNA gyrase inhibitor with potent activity against both Gram-positive and Gram-negative resistant bacteria including anaerobes.
Mitoxantrone cancer drug molecule (type II topoisomerase inhibitor). Atoms are represented as spheres and are colour coded: hydrogen (white), carbon (grey), nitrogen (blue), oxygen (red). Illustration. - Stock Image F012/9242
TY - JOUR. T1 - Novel acridine-based compounds that exhibit an anti-pancreatic cancer activity are catalytic inhibitors of human topoisomerase II. AU - Oppegard, Lisa M.. AU - Ougolkov, Andrei V.. AU - Luchini, Doris N.. AU - Schoon, Renee A.. AU - Goodell, John R.. AU - Kaur, Harneet. AU - Billadeau, Daniel D.. AU - Ferguson, David M. AU - Hiasa, Hiroshi. PY - 2009/1/14. Y1 - 2009/1/14. N2 - We have identified a small library of novel substituted 9-aminoacridine derivatives that inhibit cell proliferation of pancreatic cancer cell lines by inducing apoptosis [Goodell, J.R. et al., 2008. J. Med. Chem. 51, 179-182.]. To further investigate their antiproliferative activities, we have assessed the antiproliferative activity of these acridine-based compounds against several pancreatic cancer cell lines. All four compounds used in this study inhibited the proliferation of pancreatic cancer cell lines in vitro. In addition, we have employed a xenograft tumor model and found that these compounds also ...
F14512, a Potent Antitumor Agent Targeting Topoisomerase II Vectored into Cancer Cells via the Polyamine Transport System Jean-Marc Barret, Anna Kruczynski,
Topoisomerase II In Vivo Link Kit - quantify the activity of topoisomerase in vivo and determine how a given drug affects its predicted target using the ICE Bioassay technique. Available from TopoGEN.
Structure-activity ATPase studies with other substituted purines. To obtain information concerning the mechanism of action of NSC35866, we next did structure-activity ATPase studies, including 12 other substituted purine analogues of different chemical classes ( Fig. 1). Two C9-substituted purine analogues, 9-benzylguanine and acyclovir (the latter being an inhibitor of viral DNA polymerase ref. 37), had no inhibitory effect on the ATPase reaction of human topoisomerase IIα at concentrations up to 300 μmol/L (data not shown). 6-Chloroguanine had also no inhibitory effect on the topoisomerase II ATPase reaction (data not shown).. Because NSC35866 is a S6-substituted thioether of guanine, we also assessed the ability of two other S6-substituted thioether purine analogues, 6-methylthioguanine and azathioprine (the latter being used as an antimetabolite prodrug in the clinic; ref. 38), to inhibit the topoisomerase II ATPase reaction ( Fig. 3B). Both compounds were capable of inhibiting ...
BioAssay record AID 211293 submitted by ChEMBL: Tested for inhibitory activity against Topoisomerase II isolated from HeLa cells by using SDS-K+ precipitation method.
Research is the foundation to scholarship. Research in my lab is primarily focused on the application of chemistry to solving problems related to biomolecular structure, function, and activity, especially as it relates to drug design and discovery. More precisely, we apply chemical synthesis, biological screening, and structural biology to understand the basis to molecular recognition and the physical forces that drive function.. For example, our work on opioid recognition defined the first structural models by which highly selective agonists and antagonists could be rationally designed. In the field of cancer and topoisomerase function, we designed characterized DNA binding agents that selectively inhibited topoisomerase II by threading DNA duplex and quadraplex structures thereby blocking strand cleavage. These catalytic inhibitors were further shown to avoid formation of linear DNA fragments following treatment reducing the toxic effects commonly associated with topoisomerase poisons. Using ...
Myc-DDK-tagged ORF clone of Homo sapiens topoisomerase (DNA) I, mitochondrial (TOP1MT), nuclear gene encoding mitochondrial protein as transfection-ready DNA - 10 µg - OriGene - cdna clones
HLTV.org is the leading csgo site in the world, featuring news, demos, pictures, statistics, on-site coverage and much much more!
TY - JOUR. T1 - Eukaryotic topoisomerase II preferentially cleaves alternating purine-pyrimidine repeats. AU - Spitzner, J. R.. AU - Chung, In Kwon. AU - Muller, M. T.. PY - 1990/1/11. Y1 - 1990/1/11. N2 - Alternating purine-pyrimidine sequences (RY repeats) demonstrate considerable homology to the consensus sequence for vertebrate topoisomerase II (Spitzner and Muller (1988) Nucleic Acids Res. 16: 1533-1556). This is shown below and positions that can match are underscored. (R is purine, Y is pyrimidine, K is G or T.) Topoisomerase II cleavage reactions were performed (in the absence of inhibitors) on a plasmid containing a 54 base RY repeat and the single strong cleavage site mapped to the RY repeat. Analysis of this DNA on sequencing gels showed that the enzyme cleaved a number of sites, all within the 54 base pair RY repeat. Topoisomerase II also made clustered cleavages within other RY repeats that were examined. Quantitative analysis of homology to the consensus sequence, as measured by ...
Antigen Background Topoisomerase II alpha is an essential nuclear enzyme involved in DNA replication and is a target for many anti-cancer drugs used for cancer therapy. Decreased expression of topoisomerase II alpha is the predominant mechanism of resistance to several chemotherapeutic agents. A significant variation in the range of expression of this protein has been reported in many different tumors. Reports of the analysis of primary breast tumors have indicated that topoisomerase II beta is more widely expressed than topoisomerase II alpha. Topoisomerase II alpha expression and activity is linked to the cell cycle and is associated with the proliferation status of cells.. ...
The acquisition of resistance to anticancer drugs is a key obstacle to successful cancer therapy. An increasing number of studies have investigated the roles of microRNAs in drug resistance. We previously reported that the upregulation of miR-135b and miR-196b correlated positively with acquired drug resistance in the human T-cell leukemia cell line, CCRF-CEM (CEM), and that the elevation of expression of these two microRNAs in response to the DNA damaging agent etoposide appears to be histiotype-specific (T-T Ho et al, Proceedings of the 102nd Annual Meeting of the AACR 2011). To develop a mechanistic understanding of why these microRNAs are differentially expressed, we have studied miR-196b, which maps between the HoxA9 and HoxA10 genes on chromosome 7p15.2, suggesting that miR-196b and HoxA genes might be co-activated. Indeed, we found upregulation of HoxA9 mRNA after short-term (48 h) exposure of CEM cells to the topoisomerase II inhibitors etoposide and doxorubicin. Of note, we also found ...
In yeast, a single copy of topo II is essential for chromosome segregation (Uemura et al., 1987). In the biochemical and immunological depletion study of Xenopus egg extracts, topo IIα was shown to be required for chromosome condensation, whereas the function of topo IIβ remained obscure because its localization and relative amount to topo IIα in the egg extracts were unknown (Hirano and Mitchison, 1993). In mammals, the role of topo IIα and topo IIβ, and their cellular localization, were extensively studied using specific mAbs against each isoform (Cobb et al., 1999; Tsutsui et al., 2001; Turley et al., 1997; Yabuki et al., 1996). This idea was challenged by the recent observation that there might exist residual but sizable amounts of heterodimers of topo IIα/topo IIβ in the cultured cell extract (Christensen et al., 2002).. The knocking-out of topo IIβ does not affect embryonic development because topo IIα can substitute for it until the birth of the fetus (Yang et al., 2000), ...
Inhibits the supercoiling activity of DNA gyrase. Acts by inhibiting DNA gyrase at an early step, prior to (or at the step of) binding of DNA by the gyrase. It protects cells against toxins that target DNA gyrase, by inhibiting activity of these toxins and reducing the formation of lethal double-strand breaks in the cell. Protects cells against the natural plasmid-encoded toxins microcin B17 (MccB17) and CcdB, and synthetic quinolones. Can also protect cells against alkylating agents that act independently of DNA gyrase, suggesting a more general role in protecting cells against DNA damage.
Pla, D., Sischka, A., Albericio, F., Alvarez, M., Fernandez-Busquets, X., & Anselmetti, D. (2009). Optical-Tweezers Study of Topoisomerase Inhibition. Small, 5(11), 1269-1272. doi:10.1002/smll. ...
The Topo II inhibitor etoposide has been administered to women during pregnancy, with healthy babies born, although there are no data on the side-effects of etoposide on the reproductive system of these children, as none have yet reached puberty. Our results, using in vitro systems to assess the effects of etoposide, show that exposure of pre-follicular ovaries to etoposide results in a near-complete elimination of healthy follicles by the end of culture. This observed lack of follicles is a direct result of etoposide-treated pre-follicular germ cells failing to survive, with only a small proportion capable of forming follicles. Etoposide was used in concentrations considerably lower than those measured in the serum of patients, concentrations of 50-150 ng ml−1 being used, compared with 5-60 μg ml−1 in patient serum [38]. In contrast, exposure to oocytes once they were enclosed in follicles had no effect on total follicle numbers or health, the only effect seen on transitional follicles, ...
Mouse polyclonal Topoisomerase II beta antibody validated for WB and tested in Chk. With 2 independent reviews. Immunogen corresponding to synthetic peptide
We selected and characterized a 30-fold etoposide (VP-16)-resistant subline of K562 human leukemia cells (K/VP.5) that exhibits quantitative and qualitative changes in topoisomerase II, including hypophosphorylation of this drug target. The initial rate of topoisomerase II phosphorylation was reduced 3-fold in K/VP.5 compared with K562 cells, but the rate of dephosphorylation was similar. Analysis of potential topoisomerase II protein kinases revealed a 3-fold reduction in the level of the beta II protein kinase C (PKC) in K/VP.5 cells, whereas levels of alpha- and epsilon PKC, casein kinase II, p42map kinase, and p34cdc2 kinase were comparable for both cell lines. The PKC activator, bryostatin 1, together with K562 nuclear extracts potentiated VP-16-induced topoisomerase II/DNA covalent complex formation in nuclei isolated from K/VP.5 cells but not from K562 cells. Bryostatin 1 effects were blocked by the PKC inhibitor 7-O-methyl-hydroxy-staurosporine. Bryostatin 1 also up-regulated ...
Anticancer Drug Action Lab of Scott H. Kaufmann, M.D., Ph.D., at Mayo Clinic: Cellular Responses to DNA Damage Induced by Topoisomerase Poisons.
Introduction: Vorinostat has been shown to potentiate DNA damage induced by topoisomerase II inhibitors in a sequence dependent fashion. A multi-center, open label phase I study with escalating doses of vorinostat in combination with etoposide was conducted to establish the safety of the combination in pediatric patients with refractory solid tumors to determine the maximum tolerated dose (MTD), dose limiting toxicity (DLT) and recommended phase II dose (RP2D) of this regimen.. Methods: Eligible patients were ≤21 years of age with relapsed/refractory solid tumors including central nervous system tumors. Study design consisted of a standard 3+3 dose escalation schema. Vorinostat was administered once daily for days 1-4 of the treatment cycle in escalating doses (125 mg/m2, 160 mg/m2, 210 mg/m2, and 270 mg/m2). Etoposide was administered at a fixed dose of 100 mg/m2/day on days 3-5 of the treatment cycle. Etoposide was administered 4 hours after administration of vorinostat. Each treatment cycle ...
B) HCT116 cells were treated with increasing doses of SN-38 and treated with 4 nM SN-38 for different time. Cell extracts were prepared and analyzed by Western blotting with indicated antibody. These experiments were repeated thrice. (C) HCT116 cells were transfected with 2 μg of EGFP-LC3 construct. At 8 h post-transfection, cells were treated with 4 nM of SN-38 for 48 h. And then cells were examined by confocal microscopy (magnification × 400). The percentage of cells showing accumulation of EGFP-LC3 in puncta (EGFP-LC3vac) was quantified. (D) LOVO and HCT116 cells were treated with 2 nM and 4 nM of SN-38 combined with 10 mM of 3-Methyladenine (3-MA) for 48 h respectively. Cell extracts were prepared and analyzed by Western blotting with indicated antibody. These experiments were repeated thrice. (E) Cells were treated with indicated concentrations of 3-MA and SN-38 for 48 h. Cell apoptosis was assessed by Annexin V-FITC/PI staining assay by flow cytometry. Columns, means of three ...
The phosphatidylinositol 3-kinase (PI3K) enzyme is an obligate heterodimer composed of a regulatory subunit (p85) and a catalytic subunit (p110) (1). The inter-SH2 domain of p85 binds to both the adapter-binding domain and the C2 domain of p110, causing its stabilization and catalytic inhibition, respectively (2). Once recruited to the membrane by the interaction of p85 with a variety of receptors, p110 is activated through a conformational switch and produces phosphatidylinositol 3,4,5-trisphosphate (PIP3), which functions as a cellular second messenger. PIP3 recruits kinases containing a pleckstrin homology domain to the cell membrane, where they are activated. These kinases, the most important of which is AKT, control a multitude of pathways, including cell growth, survival, and metabolism (3). The tumor suppressor lipid phosphatase PTEN hydrolyzes PIP3 to PIP2, thus acting as a functional antagonist of PI3K (4).. Given the range of biological processes controlled by PI3K, it is not ...
3RAF: Inhibitor-stabilised cleavage complexes of topoisomerase IIa: structural analysis of drug-dependent inter- and intramolecular interactions
Six long chain fatty acid esters of quercetin-3-O-glucoside (Q3G) acylated enzymatically were used for determining their antiproliferative action in comparison to precursor compounds (quercetin, Q3G and six fatty acids namely, stearic acid, oleic acid, linoleic acid, alpha-linolenic acid, eicosapentaenoic and docosahexanoic acids) using HepG2 cells. Long chain fatty acid esters of Q3G showed significant inhibition of cell proliferation (approximately 85% to 90%) compared to the precursor compounds and two prescribed anticancer-drugs (Sorafenib and Cisplatin) after 6 hrs and 24 hrs by inducing cell cycle arrest, apoptosis and DNA topoisomerase II inhibition. Among the six fatty acid esters of Q3G, oleic acid ester (OA-Q3G) displayed the greatest anti-proliferation action and upon further investigation showed significant regulation of expression of genes involved in cell cycle, growth, survival and apoptosis at gene and protein level. Overall, results of the study suggest strong potential of these ...
The accumulation of weakly basic drugs into acidic organelles has recently been described as a contributor to resistance in childhood cancer rhabdomyosarcoma (RMS) cell lines with differential sensitivity to a novel topoisomerase II inhibitor, AS-DACA. The current study aims to explore the contribution of the endocytic pathway to AS-DACA sequestration in RMS cell lines. A 24-fold differential in AS-DACA cytotoxicity was detected between the RMS lines RD and Rh30. The effect of inhibitors of the endocytic pathway on AS-DACA sensitivity in RMS cell lines, coupled with the variations of endosomal marker expression, indicated the late endosomal/lysosomal compartment was implicated by confounding lines of evidence. Higher expression levels of Lysosomal-Associated Membrane Protein-1 (LAMP1) in the resistant RMS cell line, RD, provided correlations between the increased amount and activity of these compartments to AS-DACA resistance. The late endosomal inhibitor 3-methyladenine increased AS-DACA sensitivity
An N-formamido pyrrole- and imidazole-containing triamide (f-PIP) has been shown by DNase I footprinting, SPR, and CD studies to bind as a stacked dimer to its cognate sequences: 5-TACGAT-3 (5-flank of the inverted CCAAT box-2 of the human topoisomerase IIalpha promoter) and 5-ATCGAT-3. A gel shift experiment provided evidence for f-PIP to inhibit protein-DNA interaction at the ICB2 site. Western blot studies showed that expression of the topoisomerase IIalpha gene in confluent NIH 3T3 cells was induced by treatment with f-PIP. The results suggested that the triamide was able to enter the nucleus, interacted with the target site within ICB2, inhibited NF-Y binding, and activated gene expression.. ...
Both occupational exposure to the leukemogen benzene and in vitro exposure to its metabolite hydroquinone (HQ) lead to the induction of numerical and structural chromosome changes. Several studies have shown that HQ can form DNA adducts, disrupt microtubule assembly and inhibit DNA topoisomerase II (topo II) activity. As these are potential mechanisms underlying endoreduplication (END), a phenomenon that involves DNA amplification without corresponding cell division, we hypothesized that HQ could cause END. We measured END in the human lymphoblastoid cell line, TK6, treated with HQ (0-20 µM) and etoposide (0-0.2 µM) for 48 h. Etoposide was used as a positive control as it is a topo II poison and established human leukemogen that has previously been shown to induce END in Chinese hamster ovary cells. Both HQ and etoposide significantly induced END in a dose-dependent manner (Ptrend , 0.0001 and Ptrend = 0.0003, respectively). Since END may underlie the acquisition of high chromosome numbers by ...
The focus of this investigation is about DNA topoisomerases, the molecular targets of clinically important chemotherapy, and mechanisms of drug resistance in human myeloma and leukemia cell lines. The ultimate goal of this investigation was to identify mechanism(s) of drug resistance to anticancer agents so that a strategy to overcome drug resistance could be conceived. We established an in vitro cell model by using human leukemia and myeloma cell lines to investigate possible mechanisms of drug resistance that are observed in confluent cells. Plateau cell densities demonstrated de novo drug resistance to commonly used chemotherapeutic agents that was independent of altered drug transport. We established that cellular drug resistance in these cells is a function of topo IIalpha subcellular localization and further demonstrate that topo IIalpha translocates to the cytoplasm in a cell-density dependent manner. We provide experimental data that supports the nuclear export of topo IIalpha as the most likely
Topological problems of DNA may arise in the course of cellular processes such as DNA replication, transcription, recombination, repair, chromosome segregation, and maintenance of chromosome structure. During these events, torsional strain of double-strand DNA leads to supercoiling, which inevitably interferes with biological functions. DNA topoisomerases are the enzymes that resolve such problems by catalyzing the concerted breakage and rejoining of DNA strands (1). Two major topoisomerases, topoisomerase I and topoisomerase II, have been identified in all eukaryotic cells; the former type catalyzes the passage of the DNA strand through a transient single-strand break, whereas the latter catalyzes the passage of DNA double strands through a transient double-strand break (1).. In addition to their cellular function, both topoisomerase I and topoisomerase II have generated extensive clinical interest in chemotherapy. There is good evidence that topoisomerases are the principal intracellular ...
Drugs that inhibit the action of topoisomerase enzymes (regulatory enzymes that catalyze the breakage and religation of DNA) are an important class of anticancer drugs. The drugs bind reversibly to form ternary drug/DNA/enzyme complexes that result in cytotoxic DNA breaks, primarily by preventing the relegation step. The drugs are usually classified by their spectrum of inhibition, as inhibitors of topo I, topo II, or of both enzymes (dual topo I/II inhibitors). The majority of the topo II and dual topo I/II inhibitors are DNA intercalators, where a flat polyaromatic drug chromophore intercalates between the base pairs, driven primarily by stacking and electrostatic interactions. There is also a substantial and diverse class of drugs with little direct DNA affinity but which nevertheless form ternary complexes. Inhibitors of topo I are primarily of the latter type, most being analogues of the natural product camptothecin. The major deficiencies of this class are the instability of the essential ...
Leukemia is a prevalent disease affecting many people worldwide. Although chemotherapy can reverse leukemia, cells readily become resistant to the chemotherapeutic drugs used, hindering the success of the treatment. Therefore, it is necessary to understand the origins of anticancer drug resistance. Numerous cell culture models of acquired resistance to anticancer drugs have been studied. For example, the etoposide-resistant K562 leukemia cell line K/VP.5, shows decreased levels of topoisomerase II protein (the primary target of etoposide) and its mRNA (Ritke and Yalowich, 1993). Topoisomerase II is a DNA binding protein that is required for DNA replication and mitosis, so understanding its regulation is of interest to these cellular processes as well as to understanding acquired resistance to topoisomerase II targeting anticancer drugs. The overall goal of our research was two-fold. First, we isolated and sequenced the proximal K/VP.5 topoisomerase II gene promoter to look for a mutation that ...
What is the difference between Topoisomerase I and II? Topoisomerase I cuts one strand in double-stranded DNA while Topoisomerase, II cuts both strands in DNA
DNA topoisomerase II (Topo II) is essential for preventing tangling of double-stranded DNA during processes such as replication, recombination and transcription. It also associates with chromosomes at mitosis, but its roles in regulation of mitotic chromosome dynamics are the subject of considerable debate. William Earnshaw, Mar Carmena and co-workers have therefore examined the effect of knocking down Topo II by RNA interference in Drosophila S2 cells (see. p. 4715). Their studies confirm that Topo II is required for sister chromatid separation. It is not needed for kinetochore assembly but does appear to function in chromosome condensation - chromosomes in the knocked down cells are significantly less condensed than they should be. Perhaps the most interesting effect of knocking down Topo II, however, is on chromosomes aligned at the metaphase plate: their arms frequently protrude out towards the spindle poles, while the kinetochores remain at the plate. This suggests that Topo II has ...
Polyamine analogues have been shown to have antitumor activity as single agents in multiple experimental model systems (7, 8, 9, 10, 11, 12, 13, 14) . Their ability to modulate response to chemotherapeutic agents is worthy of study. This study addressed the activity of two polyamine analogues, CPENSpm and CHENSpm, in combination with multiple chemotherapeutic agents in breast cancer cell lines. The chemotherapeutic agents used were selected because they: (a) have antitumor activity in breast cancer; (b) are currently in use in the treatment of breast cancer; and (c) represent a broad spectrum of mechanisms of action. They include alkylating agents (4HC), topoisomerase II inhibitors (doxorubicin), antimetabolites (5-FU and FdURd), antimitotic agents (vinorelbine, paclitaxel, and docetaxel), and the DNA-reactive agent, c-DDP, which causes both intra- and interstrand DNA adducts.. Synergistic combinations were identified using one or both of the polyamine analogues in all of the cell lines ...
DNA Gyrase- Often referred to simply as gyrase, is an enzyme that relieves strain while double-strand DNA is being unwound by helicase. It is also known as DNA topoisomerase II. This causes negative supercoiling of the DNA. Bacterial DNA gyrase is the target of many antibiotics, including fluoroquinolones.. Dysautonomia- Also known as autonomic dysfunction, autonomic neuropathy. A a type of neuropathy affecting the nerves that carry information from the brain and spinal cord to the heart, bladder, intestines, sweat glands, pupils, and blood vessels .. ECG (Electrocardiography) - the process of recording the electrical activity of the heart over a period of time using electrodes placed on a patients body. These electrodes detect the tiny electrical changes on the skin that arise from the heart muscle depolarizing during each heartbeat.. EEG (electroencephalogram)- A test that measures and records the electrical activity of your brain.. EHR (Electronic Health Record)- An official health record ...
Various researches about doxorubicin work mechanism have done. Anthracyclin antibiotic like doxorubicin has cytotoxic action mechanism through four mechanism, that are: (1) Inhibition of topoisomerase II. (2) Intercalation of DNA so that cause DNA and RNA synthesis inhibition. (3) Cell membrane binding which cause ion flow and transport. (4) Formation of semiquinon free radicals and oxygen free radicals through iron dependent processes and reductive process that is mediated enzyme. This free radicals mechanism has known responsible in cardiotoxicity cause antracyclin antibiotic (Bruton et al, 2005). Doxorubicin can intercalation with DNA, it will directly affect transcription and replication. Doxorubicin can form complex tripartite with topoisomerase II and DNA. Topoisomerase II is an enzyme dependent ATP that work to bind DNA and cause double-stand break in the tip 3phosphate so that allowing strand exchange and streamlining the supercoiled DNA. The streamlining of this strand is followed by ...
Transient or long-term DNA self-assembly participates in essential genetic functions. The present review focuses on tight DNA-DNA interactions that have recently been found to play important roles in both controlling DNA higher-order structures and their topology. Due to their chirality, double helices are tightly packed into stable right-handed crossovers. Simple packing rules that are imposed by DNA geometry and sequence dictate the overall architecture of higher order DNA structures. Close DNA-DNA interactions also provide the missing link between local interactions and DNA topology, thus explaining how type II DNA topoisomerases may sense locally the global topology. Finally this paper proposes that through its influence on DNA self-assembled structures, DNA chirality played a critical role during the early steps of evolution.
Your Search Returned No Results.. Sorry. There is currently no product that acts on isoform Topoisomerase together.. Please try each isoform separately.. ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
The D2 sequence of the helix differs only at the thermophile valin was replaced for isoleucine in the mesophile. Both models of the mesophilic Doxorubicin Topoisomerase inhibitor and thermophilic D helices of the D1 and D2 proteins were placed in the..
In LANCE Ultra kinase assays, the binding of a Eu-labeled anti-phosphosubstrate antibody to the phosphorylated ULight-labeled substrate brings donor and acceptor molecules into close proximity. After irradiation of the kinase reaction at 320 or 340 nm, the energy from the Eu donor is transferred to the ULight acceptor dye, which in turn generates light at 665 nm. The intensity of the light emission is proportional to the level of ULight-substrate phosphorylation.. ...
Structural and kinetic characteristics of FGFR1 complexes with the type I andtype II inhibitors PDA and ponatinib.(a) Chemical structures of PDA and ponatinib.
Hey, I just have a quick question. Why would you want slow acting poison? What does it do? I mean, do you get more points compared to regular poison/ fast acting poison? And does fast acting poison get less points then both? Thanks.
The problem of poisons is considered, and it is concluded that a false dichotomy exists between poisonous and non-poisonous chemicals.