ArticlePLoS computational biology2011
A switching mechanism in doxorubicin bioactivation can be exploited to control doxorubicin toxicity.
Article in PLoS computational biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 49 citations in OpenAlex.
- Role of Endogenous Myoglobin in Anthracycline Response in Breast Cancer.Biomolecules · 2026Article
- Ferroptotic- and non-ferroptotic mechanisms associated with doxorubicin-induced male reproductive dysfunction.Toxicology reports · 2025Review
- Anticancer Potential of Quercetin on Oral Squamous Cell Carcinoma: A Scoping Review and Molecular Docking.European journal of dentistry · 2025Article
- Assessment of the Impact of Carvedilol Administered Together with Dexrazoxan and Doxorubicin on Liver Structure and Function, Iron Metabolism, and Myocardial Redox System in Rats.International journal of molecular sciences · 2024Article
- Ferroptosis-induced Cardiotoxicity and Antitumor Drugs.Current medicinal chemistry · 2024Review
- Dual-Multivalent Aptamer-Based Drug Delivery Platform for Targeted SRC Silencing to Enhance Doxorubicin Sensitivity in Endometrial Cancer.International journal of biological sciences · 2024Article
- Chemotherapy-Mediated Neuronal Aberration.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Relevance of Ferroptosis to Cardiotoxicity Caused by Anthracyclines: Mechanisms to Target Treatments.Frontiers in cardiovascular medicine · 2022Review
- Understanding the Protective Role of Exosomes in Doxorubicin-Induced Cardiotoxicity.Oxidative medicine and cellular longevity · 2022Review
- Date Palm Pollen Extract Avert Doxorubicin-Induced Cardiomyopathy Fibrosis and Associated Oxidative/Nitrosative Stress, Inflammatory Cascade, and Apoptosis-Targeting Bax/Bcl-2 and Caspase-3 Signaling Pathways.Animals : an open access journal from MDPI · 2021Article
- Systems Biology Approaches to Enzyme Kinetics.Methods in molecular biology (Clifton, N.J.) · 2021Review
- Synergistic Cotreatment Potential of Soursop (Iranian journal of pharmaceutical research : IJPR · 2021Article
- Shenmai injection suppresses multidrug resistance in MCF-7/ADR cells through the MAPK/NF-κB signalling pathway.Pharmaceutical biology · 2020Article
- Redox Systems Biology: Harnessing the Sentinels of the Cysteine Redoxome.Antioxidants & redox signaling · 2020Review
- Protective Effect of Methylxanthine Fractions Isolated fromBioMed research international · 2020Article
- Article
- Synergy of Chemo- and Photodynamic Therapies with CNanomaterials (Basel, Switzerland) · 2019Article
- Modulators of Redox Metabolism in Head and Neck Cancer.Antioxidants & redox signaling · 2018Review
- Genome-Scale Modeling of NADPH-Driven β-Lapachone Sensitization in Head and Neck Squamous Cell Carcinoma.Antioxidants & redox signaling · 2018Article
- Radiation-Sensitive Dendrimer-Based Drug Delivery System.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2018Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Although doxorubicin toxicity in cancer cells is multifactorial, the enzymatic bioactivation of the drug can significantly contribute to its cytotoxicity. Previous research has identified most of the components that comprise the doxorubicin bioactivation network; however, adaptation of the network to changes in doxorubicin treatment or to patient-specific changes in network components is much less understood. To investigate the properties of the coupled reduction/oxidation reactions of the doxorubicin bioactivation network, we analyzed metabolic differences between two patient-derived acute lymphoblastic leukemia (ALL) cell lines exhibiting varied doxorubicin sensitivities. We developed computational models that accurately predicted doxorubicin bioactivation in both ALL cell lines at high and low doxorubicin concentrations. Oxygen-dependent redox cycling promoted superoxide accumulation while NADPH-dependent reductive conversion promoted semiquinone doxorubicin. This fundamental switch in control is observed between doxorubicin sensitive and insensitive ALL cells and between high and low doxorubicin concentrations. We demonstrate that pharmacological intervention strategies can be employed to either enhance or impede doxorubicin cytotoxicity in ALL cells due to the switching that occurs between oxygen-dependent superoxide generation and NADPH-dependent doxorubicin semiquinone formation.
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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.