ArticleThe Journal of biological chemistry2012
Rac1 protein signaling is required for DNA damage response stimulated by topoisomerase II poisons.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 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
39 citing papers in PubMed, 84 citations in OpenAlex.
- RAC1 signaling in polyploid giant cancer cells: Implications for tumorigenesis and therapy resistance.Cancer letters · 2026Review
- Discovery of an Endonuclease G-inhibitory Ku80-peptide protecting against leukemogenic rearrangements at the MLL breakpoint cluster.Nature communications · 2026Article
- Overcoming acquired doxorubicin resistance of ovarian carcinoma cells by verapamil‑mediated promotion of DNA damage‑driven cytotoxicity.International journal of oncology · 2026Article
- Breast cancer cell coculture induces normal lung fibroblast transition to CAFs, promoting tumor cell dormancy and therapy resistance.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Drug Repositioning in Doxorubicin-Induced Cardiotoxicity Protection.International journal of molecular sciences · 2025Review
- CDCP1-targeting ADC outperforms standard therapies in Ras-mutant pancreatic cancer.Molecular therapy. Oncology · 2025Article
- Article
- Statins for the Primary Prevention of Anthracycline Cardiotoxicity: A Comprehensive Review.Current oncology reports · 2024Review
- Statins in Mitigating Anticancer Treatment-Related Cardiovascular Disease.International journal of molecular sciences · 2024Review
- α-Bisabolol: A Dietary Sesquiterpene that Attenuates Apoptotic and Nonapoptotic Cell Death Pathways by Regulating the Mitochondrial Biogenesis and Endoplasmic Reticulum Stress-Hippo Signaling Axis in Doxorubicin-Induced Acute Cardiotoxicity in Rats.ACS pharmacology & translational science · 2024Article
- The Role of Insulin-like Growth Factor Binding Protein (IGFBP)-2 in DNA Repair and Chemoresistance in Breast Cancer Cells.Cancers · 2024Article
- Deep learning-assisted high-content screening identifies isoliquiritigenin as an inhibitor of DNA double-strand breaks for preventing doxorubicin-induced cardiotoxicity.Biology direct · 2023Article
- Article
- An Ethanol Extract ofNutrients · 2023Article
- Cardio-Oncology: Mechanisms, Drug Combinations, and Reverse Cardio-Oncology.International journal of molecular sciences · 2022Review
- DOCK7 protects against replication stress by promoting RPA stability on chromatin.Nucleic acids research · 2021Article
- A Fibrinogen Alpha Fragment Mitigates Chemotherapy-InducedFrontiers in oncology · 2021Article
- Coordination between Cell Motility and Cell Cycle Progression in Keratinocyte Sheets via Cell-Cell Adhesion and Rac1.iScience · 2020Article
- Paradoxical Role of AT-rich Interactive Domain 1A in Restraining Pancreatic Carcinogenesis.Cancers · 2020Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To investigate the potency of the topoisomerase II (topo II) poisons doxorubicin and etoposide to stimulate the DNA damage response (DDR), S139 phosphorylation of histone H2AX (γH2AX) was analyzed using rat cardiomyoblast cells (H9c2). Etoposide caused a dose-dependent increase in the γH2AX level as shown by Western blotting. By contrast, the doxorubicin response was bell-shaped with high doses failing to increase H2AX phosphorylation. Identical results were obtained by immunohistochemical analysis of γH2AX focus formation, comet assay-based DNA strand break analysis, and measuring the formation of the topo II-DNA cleavable complex. At low dose, doxorubicin activated ataxia telangiectasia mutated (ATM) but not ATM and Rad3-related (ATR). Both the lipid-lowering drug lovastatin and the Rac1-specific inhibitor NSC23766 attenuated doxorubicin- and etoposide-stimulated H2AX phosphorylation, induction of DNA strand breaks, and topo II-DNA complex formation. Lovastatin and NSC23766 acted in an additive manner. They did not attenuate doxorubicin-induced increase in p-ATM and p-Chk2 levels. DDR stimulated by topo II poisons was partially blocked by inhibition of type I p21-associated kinases. DDR evoked by the topoisomerase I poison topotecan remained unaffected by lovastatin. The data show that the mechanisms involved in DDR stimulated by topo II poisons are agent-specific with anthracyclines lacking DDR-stimulating activity at high doses. Pharmacological inhibition of Rac1 signaling counteracts doxorubicin- and etoposide-stimulated DDR by disabling the formation of the topo II-DNA cleavable complex. Based on the data we suggest that Rac1-regulated mechanisms are required for DNA damage induction and subsequent activation of the DDR following treatment with topo II but not topo I poisons.
Indexed as
Identifiers
What OpenQuestion holds
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.