ArticleBritish journal of pharmacology2015
The catalytic topoisomerase II inhibitor dexrazoxane induces DNA breaks, ATF3 and the DNA damage response in cancer cells.
Article in British journal of pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 46 citations in OpenAlex.
- Interim Analysis of the Phase II Study: Noninferiority Study of Doxorubicin with Upfront Dexrazoxane plus Olaratumab for Advanced or Metastatic Soft-Tissue Sarcoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Trial
- Prospective Evaluation of Doxorubicin Cardiotoxicity in Patients with Advanced Soft-tissue Sarcoma Treated in the ANNOUNCE Phase III Randomized Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Trial
- The MAPK/ATF3/ASNS axis drives amino acid metabolic reprogramming to promote NSCLC survival under glucose deprivation.Journal of translational medicine · 2026Article
- Temporal Dynamics of Extracellular Matrix Remodeling in Anthracycline-Induced Cardiotoxicity.Cells · 2025Review
- Alpha-synuclein regulates nucleolar DNA double-strand break repair in melanoma.Science advances · 2025Article
- FNDC5/irisin mitigates the cardiotoxic impacts of cancer chemotherapeutics by modulating ROS-dependent and -independent mechanisms.Redox biology · 2025Article
- Activating transcription factor 3 induces oxidative stress and genotoxicity, transcriptionally modulating metastasis-related gene expression in human papillomavirus-infected cervical cancer.Virology journal · 2025Article
- Synthetic and semi-synthetic antioxidants in medicine and food industry: a review.Frontiers in pharmacology · 2025Review
- Exploring the effects of topoisomerase II inhibitor XK469 on anthracycline cardiotoxicity and DNA damage.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Inflammatory Reprogramming Mediates Changes in Three-Dimensional Strain Capacity and Cardiac Function in Beagle Dogs with Doxorubicin-Related Cardiomyopathy.Reviews in cardiovascular medicine · 2024Article
- Alpha-synuclein regulates nucleolar DNA double-strand break repair in melanoma.bioRxiv : the preprint server for biology · 2024Article
- Circular RNA Ubiquitin-associated Protein 2 Silencing Suppresses Bladder Cancer Progression by Downregulating DNA Topoisomerase 2-alpha Through Sponging miR-496.European urology open science · 2023Article
- Chalcone Derivative CX258 Suppresses Colorectal Cancer via Inhibiting the TOP2A/Wnt/β-Catenin Signaling.Cells · 2023Article
- Analysis of two-gene signatures and related drugs in small-cell lung cancer by bioinformatics.Open medicine (Warsaw, Poland) · 2023Article
- High-throughput small molecule screen identifies inhibitors of microsporidia invasion and proliferation in C. elegans.Nature communications · 2022Article
- Acridine BasedMolecules (Basel, Switzerland) · 2022Article
- Topoisomerase I inhibition and peripheral nerve injury induce DNA breaks and ATF3-associated axon regeneration in sensory neurons.Cell reports · 2021Article
- Propofol modulates the proliferation, invasion and migration of bladder cancer cells through the miR‑145‑5p/TOP2A axis.Molecular medicine reports · 2021Article
- Metabolic Aspects of Anthracycline Cardiotoxicity.Current treatment options in oncology · 2021Review
- Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeThe catalytic topoisomerase II inhibitor dexrazoxane has been associated not only with improved cancer patient survival but also with secondary malignancies and reduced tumour response. EXPERIMENTAL APPROACH: We investigated the DNA damage response and the role of the activating transcription factor 3 (ATF3) accumulation in tumour cells exposed to dexrazoxane. KEY
resultsDexrazoxane exposure induced topoisomerase IIα (TOP2A)-dependent cell death, γ-H2AX accumulation and increased tail moment in neutral comet assays. Dexrazoxane induced DNA damage responses, shown by enhanced levels of γ-H2AX/53BP1 foci, ATM (ataxia telangiectasia mutated), ATR (ATM and Rad3-related), Chk1 and Chk2 phosphorylation, and by p53 accumulation. Dexrazoxane-induced γ-H2AX accumulation was dependent on ATM. ATF3 protein was induced by dexrazoxane in a concentration- and time-dependent manner, which was abolished in TOP2A-depleted cells and in cells pre-incubated with ATM inhibitor. Knockdown of ATF3 gene expression by siRNA triggered apoptosis in control cells and diminished the p53 protein level in both control and dexrazoxane -treated cells. This was accompanied by increased γ-H2AX accumulation. ATF3 knockdown also delayed the repair of dexrazoxane -induced DNA double-strand breaks. CONCLUSIONS AND IMPLICATIONS: As with other TOP2A poisons, dexrazoxane induced DNA double-strand breaks followed by activation of the DNA damage response. The DNA damage-triggered ATF3 controlled p53 accumulation and generation of double-strand breaks and is proposed to serve as a switch between DNA damage and cell death following dexrazoxane treatment. These findings suggest a mechanistic explanation for the diverse clinical observations associated with dexrazoxane.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.