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Chemotherapeutic drugs inhibiting Topoisomerase 1 activity inhibit TNF-induced inflammatory gene expression

ABSTRACT: Chemotherapeutic drugs inhibiting Topoisomerase 1 activity inhibit TNF-induced inflammatory gene expression

PROVIDER: PRJNA528902 | ENA |

REPOSITORIES: ENA

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Chemotherapeutic drugs inhibiting Topoisomerase 1 activity inhibit TNF-induced inflammatory gene expression

Project description:Inhibitors of DNA topoisomerase I (TOP1), an enzyme relieving torsional stress of DNA by generating transient single-strand breaks, are clinically used to treat ovarian cancer, small cell lung cancer and cervical cancer. As torsional stress is generated by replication and transcription we tested the effects of clinically used TOP1 inhibitors Topotecan and SN-38 on TNF-induced gene expression. RNA-seq experiments showed that inhibition of TOP1 activity interfered with the vast majority of TNF-triggered genes, while interference with TOP2 activity had only a minor impact. TOP1 inhibition affected the expression of early and late induced genes and the relative strength of gene induction played no role in the sensitivity to TOP1 interfering drugs. These data raise the possibility that the inhibition of inflammatory gene expression contributes to the increased risk of infection seen in some patients treated with TOP1 inhibtors.

2019-06-22 | GSE128798 | GEO

Chemical profiling of the genome with anti-cancer drugs defines target specificities

Project description:Many anti-cancer drugs induce DNA breaks to eliminate tumor cells. The anthracycline topoisomerase II inhibitors can also evict histones. We performed a genome-wide high-resolution mapping of chemotherapeutic effects of various topoisomerase I and II inhibitors. We show that different drugs target different types of chromatin for induction of DNA damage and histone eviction. Topoisomerase inhibitors topotecan and etoposide similarly target transcriptionally active chromatin for DNA damage. Daunorubicin induces DNA breaks and evicts histones in active chromatin, thus quenching local DNA damage response. The analog aclarubicin evicts histones in H3K27me3-marked heterochromatin. These results can guide rational treatment decisions regarding these genome manipulating anti-cancer drugs. FAIRE-seq and g-H2AX ChIP-seq were performed on K562 cells after drug exposure

2015-05-10 | E-GEOD-60395 | biostudies-arrayexpress

Chemical profiling of the genome with anti-cancer drugs defines target specificities

2015-05-10 | GSE60395 | GEO

O-GlcNAcylation elevates topoisomerase IIα catalytic activity: a role in the chemotherapy resistance of breast cancer

Project description:DNA topoisomerase IIα (TOP2A) plays a vital role in replication and cell division by catalytically altering DNA topology. It is a prominent target for anticancer drugs. However, it is currently unknown whether TOP2A is O-GlcNAc-modified, and the mechanism by which interplay between TOP2A and O-GlcNAcylation affects breast cancer chemotherapeutic drug resistance remains unclear.

2023-03-31 | PXD041284 | iProX

Chemotherapeutic Drugs Inhibiting Topoisomerase 1 Activity Impede Cytokine-Induced and NF-κB p65-Regulated Gene Expression.

Project description: Not available

| S-EPMC6627772 | biostudies-literature

Control of Topoisomerase II Activity and Chemotherapeutic Inhibition by TCA Cycle Metabolites

Project description:Topoisomerase II (topo II) is essential for disentangling newly-replicated chromosomes. DNA unlinking involves the physical passage of one DNA duplex through another and depends on the transient formation of double-strand DNA breaks, a step exploited by frontline chemotherapies to kill cancer cells. Although anti-topo II drugs are efficacious, they also elicit cytotoxic side effects in normal cells; insights into how topo II is regulated in different cellular contexts is essential to improve their targeted use. Using chemical fractionation and mass spectrometry, we have discovered that topo II is subject to metabolic control through the TCA cycle. We show that TCA metabolites stimulate topo II activity in vitro and that levels of TCA flux modulate cellular sensitivity to anti-topo II drugs in vivo. Our works reveals an unanticipated connection between the control of DNA topology and cellular metabolism, a finding with important ramifications for the clinical use of anti-topo II therapies.

2021-01-21 | ST001658 | MetabolomicsWorkbench

Oxicam-type nonsteroidal anti-inflammatory drugs inhibit NPR1-mediated salicylic acid pathway

Project description:Oxicam-type nonsteroidal anti-inflammatory drugs inhibit NPR1-mediated salicylic acid pathway

| PRJNA646744 | ENA

Chemotherapeutic drugs inhibit ribosome biogenesis at various levels.

Project description: Not available

| S-EPMC2852979 | biostudies-literature

Co-ordinate inhibition of autism candidate genes by topoisomerase inhibitors [Seq]

Project description:Topoisomerases are necessary for the expression of neurodevelopmental genes, and are mutated in some patients with autism spectrum disorder (ASD). We have studied the effects of inhibitors of Topoisomerase 1 (Top1) and Topoisomerase 2 (Top2) enzymes on mouse cortical neurons. We find that topoisomerases selectively inhibit long genes (>100kb), with little effect on all other gene expression. Using ChIPseq against RNA Polymerase II (Pol2) we show that the Top1 inhibitor topotecan blocks transcriptional elongation of long genes specifically. Many of the genes inhibited by topotecan are candidate ASD genes, leading us to propose that topoisomerase inhibition might contribute to ASD pathology. [Mouse] 5 biological replicates of transcriptome sequencing (RNAseq) from topotecan treated neurons and vehicle treated controls; Pol2 ChIPseq of topotecan and vehicle treated neurons [Human] Transcriptome sequencing (RNAseq) from topotecan treated neurons and vehicle treated control.

2013-08-30 | E-GEOD-43526 | biostudies-arrayexpress

Co-ordinate inhibiton of autism candidate genes by topoisomerase inhibitors [array]

2013-08-30 | GSE43899 | GEO

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