ArticleThe Journal of clinical investigation2007
Telomere damage induced by the G-quadruplex ligand RHPS4 has an antitumor effect.
Article in The Journal of clinical investigation, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.
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Who cites it
101 citing papers in PubMed, 252 citations in OpenAlex.
- Redox regulation of telomerase and telomeres in cancer: a critical appraisal of exposure, causality and molecular directness.Molecular biology reports · 2026Review
- Dibenzoacridinium derivatives: a new class of G-quadruplex ligands with anti-HIV-1 properties.RSC medicinal chemistry · 2026Article
- Detangling knots: the intricate roles of G-quadruplexes in herpesvirus replication.Journal of virology · 2026Review
- Review
- CTCF directly binds G-quadruplex structures to regulate genome topology and gene expression.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- G-quadruplex stabilization via small molecules as a potential anti-cancer strategy.Cellular & molecular biology letters · 2026Review
- HSP90 inhibition disrupts telomere maintenance and promotes chromosomal instability (CIN) in cancer cells.Research square · 2026Article
- Cigarette smoke destabilizes G-quadruplex structures and antagonizes G4-ligand effects in macrophages.Scientific reports · 2025Article
- G-quadruplexes in the proximity 3'-UTR enhances alternative polyadenylation of Neogenin 1.iScience · 2025Article
- Reversing uL3-mediated chemoresistance through synergistic combination of 5-FU and G-quadruplex ligands.NAR cancer · 2025Article
- Recent Progress and Potential of G4 Ligands in Cancer Immunotherapy.Molecules (Basel, Switzerland) · 2025Review
- Telomeres, telomerase, and cancer: mechanisms, biomarkers, and therapeutics.Experimental hematology & oncology · 2025Review
- Genes as Genome Stabilizers in Pluripotent Stem Cells.Advances in experimental medicine and biology · 2025Review
- Telomere Reprogramming and Cellular Metabolism: Is There a Link?International journal of molecular sciences · 2024Review
- From Crypts to Cancer: A Holistic Perspective on Colorectal Carcinogenesis and Therapeutic Strategies.International journal of molecular sciences · 2024Review
- A Phenotypic Approach to the Discovery of Potent G-Quadruplex Targeted Drugs.Molecules (Basel, Switzerland) · 2024Review
- Therapeutic Use of G4-Ligands in Cancer: State-of-the-Art and Future Perspectives.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Resf1 is a compound G4 quadruplex-associated tumor suppressor for triple negative breast cancer.PLoS genetics · 2024Article
- G-quadruplex-mediated genomic instability drives SNVs in cancer.Nucleic acids research · 2024Article
- G-quadruplex DNA and RNA in cellular senescence.Frontiers in aging · 2024Review
41 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 7 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Functional telomeres are required for the replicability of cancer cells. The G-rich strand of telomeric DNA can fold into a 4-stranded structure known as the G-quadruplex (G4), whose stabilization alters telomere function limiting cancer cell growth. Therefore, the G4 ligand RHPS4 may possess antitumor activity. Here, we show that RHPS4 triggers a rapid and potent DNA damage response at telomeres in human transformed fibroblasts and melanoma cells, characterized by the formation of several telomeric foci containing phosphorylated DNA damage response factors gamma-H2AX, RAD17, and 53BP1. This was dependent on DNA repair enzyme ATR, correlated with delocalization of the protective telomeric DNA-binding protein POT1, and was antagonized by overexpression of POT1 or TRF2. In mice, RHPS4 exerted its antitumor effect on xenografts of human tumor cells of different histotype by telomere injury and tumor cell apoptosis. Tumor inhibition was accompanied by a strong DNA damage response, and tumors overexpressing POT1 or TRF2 were resistant to RHPS4 treatment. These data provide evidence that RHPS4 is a telomere damage inducer and that telomere disruption selectively triggered in malignant cells results in a high therapeutic index in mice. They also define a functional link between telomere damage and antitumor activity and reveal the key role of telomere-protective factors TRF2 and POT1 in response to this anti-telomere strategy.
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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.