Gallic Acid: A Natural Phenolic Compound Exerting Antitumoral Activities in Colorectal Cancer via Interaction with G-Quadruplexes
2022
Sánchez Martín, Victoria | Plaza-Calonge, María del Carmen | Soriano-Lerma, Ana | Ortiz González, Matilde | Linde Rodríguez, Ángel | Perez-Carrasco, Virginia | Ramírez Macías, María Inmaculada | Cuadros, Marta | Gutierrez-Fernandez, Jose | Murciano-Calles, Javier | Rodríguez-Manzaneque, Juan Carlos | Soriano Rodríguez, Miguel | García Salcedo, José Antonio
Natural phenolic compounds have gained momentum for the prevention and treatment of cancer, but their antitumoral mechanism of action is not yet well understood. In the present study, we screened the antitumoral potential of several phenolic compounds in a cellular model of colorectal cancer (CRC). We selected gallic acid (GA) as a candidate in terms of potency and selectivity and extensively evaluated its biological activity. We report on the role of GA as a ligand of DNA G-quadruplexes (G4s), explaining several of its antitumoral effects, including the transcriptional inhibition of ribosomal and CMYC genes. In addition, GA shared with other established G4 ligands some effects such as cell cycle arrest, nucleolar stress, and induction of DNA damage. We further confirmed the antitumoral and G4-stabilizing properties of GA using a xenograft model of CRC. Finally, we succinctly demonstrate that GA could be explored as a therapeutic agent in a patient cohort with CRC. Our work reveals that GA, a natural bioactive compound present in the diet, affects gene expression by interaction with G4s both in vitro and in vivo and paves the way towards G4s targeting with phenolic compounds.
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