In vitro and in silico study on the impact of chlorogenic acid in colorectal cancer cells: proliferation, apoptosis, and interaction with β-Catenin and LRP6

ABSTRACT: Colorectal cancer mortality rate and highly altered proteins from the Wnt/β-catenin pathway increase the scientific community’s interest in finding alternatives for prevention and treatment. This study aims to determine the biological effect of chlorogenic acid (CGA) on two colorectal cancer cell lines, HT-29 and SW480, and its interactions with β-catenin and LRP6 to elucidate a possible modulatory mechanism on the Wnt/β-catenin pathway. These effects were determined by propidium iodide and DiOC6 for mitochondrial membrane permeability, MitoTracker cycle phases, and molecular docking for protein–ligand interactions and binding affinity. Here, it was found that CGA at 2000 μM significantly affects cell viability and causes DNA fragmentation in SW480 cells rather than in HT-29 cells, but in both cell lines, it induces ROS production. Additionally, CGA has similar affinity and interactions for LRP6 as niclosamide but has a higher affinity for both β-catenin sites than C2 and iCRT14. These results suggest a possible modulatory role of CGA over the Wnt/β-catenin pathway in colorectal cancer.

• Autores: Henao Castañeda, Isabel Cristina; Vélez Vargas, Laura Catalina; Santa González, Gloria Angélica; Pedroza Díaz, Nini Johanna; Uribe, Diego
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2023
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/40141
• Acceso en línea: https://hdl.handle.net/10495/40141
• Palabra clave: Ácido Clorogénico; Chlorogenic Acid; Neoplasias Colorrectales; Colorectal Neoplasms; Apoptosis; beta Catenina; beta Catenin; Proteína-6 Relacionada a Receptor de Lipoproteína de Baja Densidad; Low Density Lipoprotein Receptor-Related Protein-6; https://id.nlm.nih.gov/mesh/D002726; https://id.nlm.nih.gov/mesh/D015179; https://id.nlm.nih.gov/mesh/D017209; https://id.nlm.nih.gov/mesh/D051176; https://id.nlm.nih.gov/mesh/D060488
• Rights: openAccess
• License: http://creativecommons.org/licenses/by/2.5/co/