ArticlePloS one2014
RHPS4 G-quadruplex ligand induces anti-proliferative effects in brain tumor cells.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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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.
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
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Advancements in Telomerase-Targeted Therapies for Glioblastoma: A Systematic Review.International journal of molecular sciences · 2024Pooled it
- G-quadruplexes in the proximity 3'-UTR enhances alternative polyadenylation of Neogenin 1.iScience · 2025Article
- From Crypts to Cancer: A Holistic Perspective on Colorectal Carcinogenesis and Therapeutic Strategies.International journal of molecular sciences · 2024Review
- Aging, Cancer, and Inflammation: The Telomerase Connection.International journal of molecular sciences · 2024Review
- High-Speed Video Microscopy of Ependymal Cilia in Brain Organotypic and Cell Culture Models.Methods in molecular biology (Clifton, N.J.) · 2024Article
- General commentary: GQIcombi application to subdue glioma via differentiation therapy.Frontiers in oncology · 2024Article
- Cellular senescence in glioma.Journal of neuro-oncology · 2023Review
- Crosstalk between G-quadruplex and ROS.Cell death & disease · 2023Review
- Possible molecular mechanisms underlying the development of atherosclerosis in cancer survivors.Frontiers in cardiovascular medicine · 2023Review
- Exploring the Interaction of G-quadruplex Binders with a (3 + 1) Hybrid G-quadruplex Forming Sequence within the PARP1 Gene Promoter Region.Molecules (Basel, Switzerland) · 2022Article
- Review
- Telomeres: Implications for Cancer Development.International journal of molecular sciences · 2018Review
- Intragenic G-quadruplex structure formed in the human CD133 and its biological and translational relevance.Nucleic acids research · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTelomeric 3' overhangs can fold into a four-stranded DNA structure termed G-quadruplex (G4), a formation which inhibits telomerase. As telomerase activation is crucial for telomere maintenance in most cancer cells, several classes of G4 ligands have been designed to directly disrupt telomeric structure.
methodsWe exposed brain tumor cells to the G4 ligand 3,11-difluoro-6,8,13-trimethyl-8H-quino[4,3,2-kl]acridinium methosulfate (RHPS4) and investigated proliferation, cell cycle dynamics, telomere length, telomerase activity and activated c-Myc levels.
resultsAlthough all cell lines tested were sensitive to RHPS4, PFSK-1 central nervous system primitive neuroectodermal cells, DAOY medulloblastoma cells and U87 glioblastoma cells exhibited up to 30-fold increased sensitivity compared to KNS42 glioblastoma, C6 glioma and Res196 ependymoma cells. An increased proportion of S-phase cells were observed in medulloblastoma and high grade glioma cells whilst CNS PNET cells showed an increased proportion of G1-phase cells. RHPS4-induced phenotypes were concomitant with telomerase inhibition, manifested in a telomere length-independent manner and not associated with activated c-Myc levels. However, anti-proliferative effects were also observed in normal neural/endothelial cells in vitro and ex vivo.
conclusionThis study warrants in vivo validation of RHPS4 and alternative G4 ligands as potential anti-cancer agents for brain tumors but highlights the consideration of dose-limiting tissue toxicities.
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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.