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)

Interaction between tumor necrosis factor (TNF) and the DNA topoisomerase II inhibitor, etoposide VP-16, in cell killing has been studied. To accurately investigate the nature of DNA damage during the cell killing process, experiments were assessed using the highly TNF-sensitive WEHI164.13 murine fibrosarcoma clone and DNA filter elution methodology. Concomitant treatment of cells with combination of TNF/VP-16 resulted in marked enhancement of cell lysis. Using the alkaline elution technique, we show that TNF fails to induce DNA single-strand breaks as compared to those generated by VP-16. In addition, the potentiating effect of VP-16 on TNF-mediated WEHI164.13 cell killing was not associated with an increase in its intrinsic activity with respect to DNA single-strand break formation. While the 2 phospholipase A2 inhibitors, quinacrine and dexamethasone, were efficient in inhibiting TNF-mediated cell lysis, only quinacrine was efficient in selectively abrogating the TNF/VP-16 cell killing pathway. The inhibitory effect of quinacrine on VP-16/TNF-mediated cell lysis was accompanied by a marked decrease in VP-16-mediated DNA single-strand break generation. Taken together, our findings suggest that TNF and TNF/VP-16 treatments may involve different events during cell killing and support the hypothesis that 2 signals are required for optimal induction of cell lysis by the combination of VP-16/TNF: one signal provided by VP-16 resulting in topoisomerase II inhibition and subsequent DNA single-strand break generation, and a second signal involving TNF.
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PMID:Potentiation of TNF-mediated cell killing by VP-16: relationship to DNA single-strand break formation. 224 91

A molecular docking investigation has been carried out on cytotoxic prenylated flavonoids from Lonchocarpus haberi with cancer-relevant chemotherapeutic targets known to be inhibited by flavonoids. Two molecular docking programs, Molegro and ArgusDock, were used to compare the binding energies of Lonchocarpus flavonoids with other flavonoids, inhibitors, or known ligands, to aromatase (CYP 19), fatty acid synthase (FAS), xanthine oxidase (XO), cyclooxygenases (COX-1 and COX-2), lipoxygenase (LOX-3), ornithine decarboxylase (ODC), protein tyrosine kinase (PTK), phosphoinositide 3-kinase (PI3K), protein kinase C (PKC), topoisomerase II (ATP binding site), ATP binding cassette (ABC) transporter, and phospholipase A(2) (PLA). The Lonchocarpus flavonoids examined in this study exhibited docking energies comparable to or stronger than other flavonoids that had been previously shown to be effective inhibitors of these enzymes. Furthermore, prenylated flavonoids, such as the Lonchocarpus flavonoids and xanthohumol, generally showed greater binding energies than the non-prenylated flavonoids. We conclude, therefore, that the Lonchocarpus flavonoids possibly owe their cytotoxic activity by inhibition of one or more of these enzymes.
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PMID:Cancer-relevant biochemical targets of cytotoxic Lonchocarpus flavonoids: a molecular docking analysis. 1960 3