ArticlePloS one2012
Probing the dynamics of doxorubicin-DNA intercalation during the initial activation of apoptosis by fluorescence lifetime imaging microscopy (FLIM).
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 42 papers.
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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.
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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
42 citing papers in PubMed, 96 citations in OpenAlex.
- Doxorubicin-Induced Cardiotoxicity in Breast Cancer: Mechanistic Pathways, Pharmacogenomic Modifiers, and Translational Strategies.Cardiovascular toxicology · 2026Review
- Mechanistic Insights into Unary Peptide-Membrane Interactions Enable Stable Encapsulation and Trigger-Responsive Peptidyl Liposomes.Journal of the American Chemical Society · 2026Article
- New fluorescently labeled isothiocyanate derivatives as a potential cancer theranostic tool.Scientific reports · 2025Article
- Fluorescence Anisotropy for Detailed Analysis of Doxorubicin Loading into DNA Origami Nanocarriers for Drug Delivery.ACS applied nano materials · 2025Article
- In vitro cellular interaction of drug-loaded liposomes with 2D and 3D cell culture of U87-MG cell line.PloS one · 2025Article
- Mechanosensitive nuclear uptake of chemotherapy.Science advances · 2024Article
- The supramolecular processing of liposomal doxorubicin hinders its therapeutic efficacy in cells.Molecular therapy. Oncology · 2024Article
- High-throughput fluorescence lifetime imaging flow cytometry.Nature communications · 2024Article
- Quantitative imaging of doxorubicin diffusion and cellular uptake in biomimetic gels with human liver tumor cells.Drug delivery and translational research · 2024Article
- Theranostic Fluorescent Probes.Chemical reviews · 2024Review
- A review of the pathophysiological mechanisms of doxorubicin-induced cardiotoxicity and aging.npj aging · 2024Review
- Exploring doxorubicin transport in 2D and 3D models of MDA-MB-231 sublines: impact of hypoxia and cellular heterogeneity on doxorubicin accumulation in cells.American journal of cancer research · 2024Article
- Protective effect of cafestol against doxorubicin-induced cardiotoxicity in rats by activating the Nrf2 pathway.Frontiers in pharmacology · 2023Article
- Effect of Collagen Matrix on Doxorubicin Distribution and Cancer Cells' Response to Treatment in 3D Tumor Model.Cancers · 2022Article
- Nanocomposite of electrochemically reduced graphene oxide and gold nanourchins for electrochemical DNA detection.IET nanobiotechnology · 2022Article
- The Mechanism of Dynamic Interaction between Doxorubicin and Calf Thymus DNA at the Single-Molecule Level Based on Confocal Raman Spectroscopy.Micromachines · 2022Article
- Impact of Doxorubicin on Cell-Substrate Topology.International journal of molecular sciences · 2022Article
- The Employment of GeneraNutrients · 2022Review
- Synthesis and characterization of a novel pH-responsive drug-releasing nanocomposite hydrogel for skin cancer therapy and wound healing.Journal of materials chemistry. B · 2021Article
- Aptamer-Aptamer Chimera for Targeted Delivery and ATP-Responsive Release of Doxorubicin into Cancer Cells.International journal of molecular sciences · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Doxorubicin is a potent anthracycline antibiotic, commonly used to treat a wide range of cancers. Although postulated to intercalate between DNA bases, many of the details of doxorubicin's mechanism of action remain unclear. In this work, we demonstrate the ability of fluorescence lifetime imaging microscopy (FLIM) to dynamically monitor doxorubicin-DNA intercalation during the earliest stages of apoptosis. The fluorescence lifetime of doxorubicin in nuclei is found to decrease rapidly during the first 2 hours following drug administration, suggesting significant changes in the doxorubicin-DNA binding site's microenvironment upon apoptosis initiation. Decreases in doxorubicin fluorescence lifetimes were found to be concurrent with increases in phosphorylation of H2AX (an immediate signal of DNA double-strand breakage), but preceded activation of caspase-3 (a late signature of apoptosis) by more than 150 minutes. Time-dependent doxorubicin FLIM analyses of the effects of pretreating cells with either Cyclopentylidene-[4-(4-chlorophenyl)thiazol-2-yl)-hydrazine (a histone acetyltransferase inhibitor) or Trichostatin A (a histone deacetylase inhibitor) revealed significant correlation of fluorescence lifetime with the stage of chromatin decondensation. Taken together, our findings suggest that monitoring the dynamics of doxorubicin fluorescence lifetimes can provide valuable information during the earliest phases of doxorubicin-induced apoptosis; and implicate that FLIM can serve as a sensitive, high-resolution tool for the elucidation of intercellular mechanisms and kinetics of anti-cancer drugs that bear fluorescent moieties.
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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.