Evidence map›Paper›PMID 40542407›Full record

ArticleCellular & molecular biology letters2025

In-depth analysis of the mode of action of resveratrol: genome-wide characterization of G-quadruplex binding properties.

Ana Soriano-Lerma, Victoria Sánchez-Martín, Javier Murciano-Calles, Matilde Ortiz-González, María J Tello-López, Virginia Pérez-Carrasco, Ángel Linde-Rodríguez, Inmaculada Ramírez-Macías, Irene Gómez-Pìnto, Inmaculada López-Aliaga and 2 more

Abstract read
In one paragraph

Article in Cellular & molecular biology letters, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Ana Soriano-LermaGENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, 18016, Granada, Spain.
Victoria Sánchez-MartínDepartment of Biochemistry, Molecular Biology III and Immunology, University of Granada, 18016, Granada, Spain.
Javier Murciano-CallesDepartment of Physical Chemistry, Unit of Excellence for Chemistry Applied to Biomedicine and the Environment, and Institute of Biotechnology, University of Granada, 18071, Granada, Spain.
Matilde Ortiz-GonzálezCenter for Intensive Mediterranean Agrosystems and Agri-Food Biotechnology (CIAIMBITAL), University of Almeria, 04001, Almería, Spain.
María J Tello-LópezGENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, 18016, Granada, Spain.
Virginia Pérez-CarrascoGENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, 18016, Granada, Spain.
Ángel Linde-RodríguezGENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, 18016, Granada, Spain.
Inmaculada Ramírez-MacíasDepartment of Parasitology, University of Granada, 18071, Granada, Spain.
Irene Gómez-PìntoInstituto de Química Física 'Blas Cabrera', (IQF-CSIC), 28006, Madrid, Spain.
Inmaculada López-AliagaDepartment of Physiology (Faculty of Pharmacy), Institute of Nutrition and Food Technology "José Mataix", University of Granada, 18071, Granada, Spain.
Miguel Soriano *Center for Intensive Mediterranean Agrosystems and Agri-Food Biotechnology (CIAIMBITAL), University of Almeria, 04001, Almería, Spain.
Jose A Garcia Salcedo *GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, 18016, Granada, Spain. jags@genyo.es.ORCID http://orcid.org/0000-0003-3399-1835

Funding

Consejería de Economía, Conocimiento, Empresas y Universidad, Junta de Andalucía BIO-344Instituto de Salud Carlos III PI21/00497Ministerio de Ciencia, Innovación y Universidades PID2020-120481RB-I00/AEI/10.13039/50110001103
6 · The paper itself

Abstract

backgroundResveratrol (RSV) is one of the most studied and used biomolecules, for which many pharmacological effects targeting multiple tissues have been described. However, a common underlying mechanism driving its full pharmacological activity has not been described in detail. G-quadruplexes (G4s) are non-canonical nucleic acid structures found in regulatory genomic locations and involved in controlling gene transcription, telomere maintenance, or genome stability, among others. This study provides a genome-wide characterization of RSV G4-binding properties, explaining its multi-target traits.

methodsImmunofluorescence assays using a nucleolar and a G4-specific antibody were used to characterize RSV cellular effects on the nucleolus and G4 stabilization. DNA damage and cell cycle analyses were performed via western blot and flow cytometry. Breaks lLbeling In Situ and Sequencing (BLISS) was used to map double strand breaks (DSB) in response to treatment, and identify G4s targeted by RSV. mRNA sequencing was used to identify changes at the transcriptional level upon treatment and relate them to a direct targeting of G4s. Biophysical assays (circular dichroism, ultraviolet-visible [UV-Vis] titration, differential scanning calorimetry, and nuclear magnetic resonance) were used to characterize RSV-G4 interactions. Lastly, luciferase-based transcription assays were performed to confirm RSV-G4 interaction in vitro and its direct influence on gene expression.

resultsIn a cellular context, RSV treatment showed classic G4-ligand effects, such as nucleolar disassembly, inhibition of RNA polymerase I, DNA damage, and cell cycle arrest. RSV was shown to stabilize cellular G4s, which accumulated around double strand breaks in the promoters of differentially expressed genes. Upon treatment, G4 stabilization triggered DNA damage and controlled gene expression. The interaction between RSV and target G4s was confirmed in vitro by biophysical assays and through luciferase-based transcription assays.

conclusionsA G4-dependent mode of action was demonstrated as the main mechanism underlying RSV pleiotropic effects, along with the identification of target genes and G4s. This in-depth analysis of the mode of action of RSV will be helpful to improve its therapeutic potential in a wide variety of health scenarios.

Indexed as

G-QuadruplexesResveratrolCell NucleolusDNA Breaks, Double-StrandedDNA DamageHumansResveratrolDNA bindingG-quadruplexResveratrolSecondary DNA structuresSmall molecule

Identifiers

PMID40542407
PMCPMC12180162

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Registered trials

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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.