ArticleChemical research in toxicology2015
Cellular Recognition and Repair of Monofunctional-Intercalative Platinum--DNA Adducts.
Article in Chemical research in toxicology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 39 citations in OpenAlex.
- Short-Chain and Long-Chain Fatty Acid-Containing Platinum-Acridine Anticancer Prodrugs: Exploiting Alternative Mechanisms of Cellular Internalization.Journal of medicinal chemistry · 2026Article
- The arylbipyridine platinum (II) complex increases the level of ROS and induces lipid peroxidation in glioblastoma cells.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2025Article
- Platinum-Acridine Agents with High Activity in Cancers Expressing the Solute Carrier MATE1 (ACS medicinal chemistry letters · 2023Article
- Computational and Experimental Characterization of rDNA and rRNA G-Quadruplexes.The journal of physical chemistry. B · 2022Article
- DNA Adduct Detection after Post-Labeling Technique with PCR Amplification (DNA-ADAPT-qPCR) Identifies the Pre-ribosomal RNA Gene as a Direct Target of Platinum-Acridine Anticancer Agents.Chemistry (Weinheim an der Bergstrasse, Germany) · 2021Article
- Square-Planar vs. Trigonal Bipyramidal Geometry in Pt(II) Complexes Containing Triazole-Based Glucose Ligands as Potential Anticancer Agents.International journal of molecular sciences · 2021Article
- Valproic Acid Regulates HR and Cell Cycle Through MUS81-pRPA2 Pathway in Response to Hydroxyurea.Frontiers in oncology · 2021Article
- Discovery of a Chiral DNA-Targeted Platinum-Acridine Agent with Potent Enantioselective Anticancer Activity.Angewandte Chemie (International ed. in English) · 2020Article
- A membrane transporter determines the spectrum of activity of a potent platinum-acridine hybrid anticancer agent.Scientific reports · 2020Article
- MUS81 Participates in the Progression of Serous Ovarian Cancer Associated With Dysfunctional DNA Repair System.Frontiers in oncology · 2019Article
- Human Serum Albumin-Delivered [Au(PEtACS medicinal chemistry letters · 2017Article
- Large-Pore Functionalized Mesoporous Silica Nanoparticles as Drug Delivery Vector for a Highly Cytotoxic Hybrid Platinum-Acridine Anticancer Agent.Chemistry (Weinheim an der Bergstrasse, Germany) · 2017Article
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3 authors at 1 institution in 1 country.
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Abstract
The cellular recognition and processing of monofunctional-intercalative DNA adducts formed by [PtCl(en)(L)](NO3)2 (P1-A1; en = ethane-1,2-diamine; L = N-[2-(acridin-9-ylamino)ethyl]-N-methylpropionamidine, acridinium cation), a cytotoxic hybrid agent with potent anticancer activity, was studied. Excision of these adducts and subsequent DNA repair synthesis were monitored in plasmids modified with platinum using incubations with mammalian cell-free extract. On the basis of the levels of [α-(32)P]-dCTP incorporation, P1-A1-DNA adducts were rapidly repaired with a rate approximately 8 times faster (t1/2 ≈ 18 min at 30 °C) than the adducts (cross-links) formed by the drug cisplatin. Cellular responses to P1-A1 and cisplatin were also studied in NCI-H460 lung cancer cells using immunocytochemistry in conjunction with confocal fluorescence microscopy. At the same dose, P1-A1, but not cisplatin, elicited a distinct requirement for DNA double-strand break repair and stalled replication fork repair, which caused nuclear fluorescent staining related to high levels of MUS81, a specialized repair endonuclease, and phosphorylated histone protein γ-H2AX. The results confirm previous observations in yeast-based chemical genomics assays. γ-H2AX fluorescence is observed as a large number of discrete foci signaling DNA double-strand breaks, pan-nuclear preapoptotic staining, and unique circularly shaped staining around the nucleoli and nuclear rim. DNA cleavage assays indicate that P1-A1 does not act as a typical topoisomerase poison, suggesting the high level of DNA double-strand breaks in cells is more likely a result of topoisomerase-independent replication fork collapse. Overall, the cellular response to platinum-acridines shares striking similarities with that reported for DNA adduct-forming derivatives of the drug doxorubicin. The results of this study are discussed in light of the cellular mechanism of action of platinum-acridines and their ability to overcome resistance to cisplatin.
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