Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:5.99.1.2 (topoisomerase)
 9,166 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In two human cancer cell lines, the breast mcf-7 and the T-cell leukemia MOLT4, we investigated the cytotoxicity of four antineoplastic agents having different mechanisms of action. We selected doxorubicin as a DNA-topoisomerase II inhibitor, FCE24517 (a Distamycin A derivative) as a DNA minor groove binder with specificity for AT bases, melphalan as an alkylating agent and cis-platinum as an alkylating agent able to form DNA-intrastrand crosslinks. From the cytotoxicity experiments a moderately toxic (less than 10% of growth inhibition) and a highly toxic (about 75% growth inhibition) dose were selected to evaluate the expression of genes involved in cell proliferation and in cell response to extracellular insults. The expression was evaluated at early times (60 min.) and 24 hrs. after treatment. At the concentrations utilized in both cell lines we could not find any alteration in the expression of p53, gas-1 and heat shock 70. After melphalan treatment down regulation of c-myc and of the H2A histone was seen at high doses, while no significant alteration of their expression was seen with the other drugs.
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PMID:Effects of DNA damaging agents on gene expression in two human cancer cell lines. 829 34

The binding behaviour toward DNA of some minor groove binders related to distamycin was studied by means of circular dichroism. In addition their influence on the activity of topoisomerases isolated from Streptomyces noursei has been investigated. The monocationic imidazole containing ligands (lexitropsins) show a decreased affinity to AT pairs but an increased affinity to GC pairs which contrasts the AT-preferred binding of Dst-2 and Dst-3. For the monocationic triimidazole containing lexitropsin the affinity for GC over AT pairs was most pronounced. It was also found that the imidazole containing lexitropsins are inhibitors of topoisomerases. These minor groove binders interfere more strongly with the DNA gyrase activity than with the prokaryotic topoisomerase I. Our results indicate that Dst-3 most effectively inhibits gyrase and topoisomerase I activity. However, the inhibitory effect is neither related to the base pair specificity nor to the binding strength of different ligands. The mechanism of interference of minor groove binders with topoisomerase activity is more complex. It is considered that different factors, such as the nature of the ligand together with their DNA binding parameters and the target sequences of the enzymes play a role in the inhibitory effects of minor groove binders.
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PMID:Binding to DNA of selected lexitropsins and effects on prokaryotic topoisomerase activity. 839 23