@misc{10481/102981,
year = {2025},
month = {2},
url = {https://hdl.handle.net/10481/102981},
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.},
organization = {Ministry of Science and Innovation of Spain (PI21/00497)},
organization = {European Union},
organization = {PID2020-120481RB-I00/AEI/10.13039/501100011033},
organization = {Junta de Andalucía (BIO-344)},
organization = {Ministry of Science, Technological Development and Innovation of the Republic of Serbia (451‐03‐65/2024‐03/200161)},
organization = {The Government of Spain PhD fellowship FPU16/05822},
organization = {University of Almeria PhD fellowship CPRE2023-069},
publisher = {Royal Society Publishing},
keywords = {G-quadruplex},
keywords = {Histone deacetylase inhibitors},
keywords = {Transcription},
keywords = {RNA polymerase I},
keywords = {Colorectal cancer},
title = {The histone deacetylase inhibitor Scriptaid targets G-quadruplexes},
doi = {10.1098/rsob.240183},
author = {Sánchez-Martín, Victoria and Tello-López, María J. and Ortiz-Morales, Andrea and Murciano Calles, Javier and García-Salcedo, José Antonio},
}