2. Academic Validation
  3. The histone deacetylase inhibitor Scriptaid targets G-quadruplexes

The histone deacetylase inhibitor Scriptaid targets G-quadruplexes

  • Open Biol. 2025 Feb;15(2):240183. doi: 10.1098/rsob.240183.
Victoria Sanchez-Martin 1 2 3 4,  Dusan Ruzic 5,  Maria J Tello-Lopez 1 6,  Andrea Ortiz-Morales 1,  Javier Murciano-Calles 7,  Miguel Soriano 6,  Katarina Nikolic 5,  Jose Antonio Garcia-Salcedo 1 2 3
Affiliations

Affiliations

  • 1 GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, Granada 18016, Spain.
  • 2 Microbiology Unit, University Hospital Virgen de las Nieves, Granada 18014, Spain.
  • 3 Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), Granada 18012, Spain.
  • 4 Department of Biochemistry, Molecular Biology III and Immunology, University of Granada, Granada 18016, Spain.
  • 5 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Belgrade, Belgrade 11221, Serbia.
  • 6 Center for Intensive Mediterranean Agrosystems and Agri-Food Biotechnology (CIAIMBITAL), University of Almeria, Almeria 04001, Spain.
  • 7 Department of Physical Chemistry, Unit of Excellence for Chemistry Applied to Biomedicine and the Environment, and Institute of Biotechnology, University of Granada, Granada 18071, Spain.
PMID: 39965659 DOI: 10.1098/rsob.240183
Abstract

Scriptaid is a chemical compound with anti-tumoural effects due to its role as a histone deacetylase inhibitor. Despite sharing part of the chemical structure with Other ligands of G-quadruplexes (G4s), the interaction of Scriptaid with G4s has not been explored before. We synthesized Scriptaid and screened its cytotoxic activity in cellular models of colorectal Cancer (CRC). We extensively evaluated its biological activity by cell cycle, immunofluorescence, qRT-PCR and Western blot experiments. To identify the G4 targets of Scriptaid, we conducted a panel of binding assays. Here, we show that Scriptaid induced cytotoxicity, cell cycle arrest and nucleolar stress in CRC cells. Moreover, Scriptaid impaired RNA polymerase I (Pol I) transcription, stabilized G4s and caused DNA damage. Finally, we disclose that these effects were attributable to the binding of Scriptaid to G4s in ribosomal DNA. In conclusion, our work reveals that a primary impact of Scriptaid on human cells is the interaction with G4s.

Keywords

G-quadruplex; RNA polymerase I; colorectal cancer; histone deacetylase inhibitor; transcription.

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