@misc{10481/90099,
year = {2021},
month = {12},
url = {https://hdl.handle.net/10481/90099},
abstract = {Guanine quadruplexes (G4s) are non-canonical nucleic acid structures commonly found in regulatory
genomic regions. G4 targeting has emerged as a therapeutic approach in cancer. We have screened naph thalene-diimides (NDIs), a class of G4 ligands, in a cellular model of colorectal cancer (CRC). Here, we identify
the leading compound T5 with a potent and selective inhibition of cell growth by high-affinity binding to G4s in
ribosomal DNA, impairing RNA polymerase I (Pol I) elongation. Consequently, T5 induces a rapid inhibition of
Pol I transcription, nucleolus disruption, proteasome-dependent Pol I catalytic subunit A degradation and
autophagy. Moreover, we attribute the higher selectivity of carbohydrate-conjugated T5 for tumoral cells
to its preferential uptake through the overexpressed glucose transporter 1. Finally, we succinctly demon strate that T5 could be explored as a therapeutic agent in a patient cohort with CRC. Therefore, we report
a mode of action for these NDIs involving ribosomal G4 targeting.},
publisher = {Cell Chem Biol},
title = {Targeting ribosomal G-quadruplexes with naphthalene-diimides as RNA polymerase I inhibitors for colorectal cancer treatment},
doi = {10.1016/j.chembiol.2021.12.007},
author = {Sánchez Martín, Victoria and Schneider, David A and Ortiz-Gonzalez, Matilde and Soriano Lerma, Ana del Carmen and Linde-Rodriguez, Angel and Perez-Carrasco, Virginia and Gutiérrez Fernández, José and Cuadros Celorrio, Marta Eugenia and Morales Vega, Juan Carlos and González, Carlos and Soriano, Miguel and García Salcedo, José Antonio},
}