Por favor, use este identificador para citar o enlazar este ítem: https://hdl.handle.net/10495/25331
Título : Styrylcoumarin 7-SC2 induces apoptosis in SW480 human colon adenocarcinoma cells and inhibits azoxymethane-induced aberrant crypt foci formation in BALB/c mice
Autor : Herrera Ramírez, Angie
Naranjo Preciado, Tonny Williams
Maldonado Celis, María Elena
Cardona Galeano, Wilson
Moreno Quintero, Gustavo Alberto
Yepes Pérez, Andrés Felipe
metadata.dc.subject.*: Muerte Celular
Cell Death
Neoplasias Colorrectales
Colorectal Neoplasms
Fecha de publicación : 2020
Editorial : Springer
Citación : Herrera-R, A., Naranjo, T.W., Maldonado, M.E. et al. Styrylcoumarin 7-SC2 induces apoptosis in SW480 human colon adenocarcinoma cells and inhibits azoxymethane-induced aberrant crypt foci formation in BALB/c mice. Med Chem Res 29, 377–395 (2020)
Resumen : ABSTRACT: In vivo chemopreventive effects associated with hybrid molecules against colon carcinogenesis remain poorly studied. In a previous study, we showed that styrylcoumarin hybrids 3-SC1, 7-SC2 (2,7-(4-hydroxy-3,5-dimethoxystyryl)-coumarin), and 7-SC3 decrease cell viability of SW480 in a time- and concentration-dependent manner (IC50-SW480/48 h = 6.92; 1.01 and 5.33 µM, respectively) with high selectivity indices after 48 h of treatment (>400; 67.8 and 7.2, respectively). The present study investigates the mechanisms of these three styrylcoumarins to induce cell death, using an in vitro model of colon adenocarcinoma cells (SW480); besides, it evaluates anticarcinogenic properties in vivo for the most active molecule. According to the results, none of the hybrids exhibited significant changes in cell cycle distribution of SW480 cells with respect to control group (G0/G1 = 85.5%, S = 7.2%, and G2/M 7.3%), which indicates that these do not have a cytostatic effect on this cell line. Besides, they did not cause mitochondrial depolarization, suggesting an alternative source for the production of reactive oxygen species (ROS). Among the evaluated compounds, the most active molecule 7-SC2 induced a greater production of ROS in comparison with the control (p < 0.05) together with a significant increase in the expression of p53, caspase-3, and a significant reduction in the production of interleukin-6 of SW480 cells. When colon carcinogenesis was induced in Balb/c mice by intraperitoneal injections of azoxymethane, a significant reduction (p < 0.05) in the number of preneoplastic lesions of mice treated with styrylcoumarin hybrid 7-SC2 was observed with regard to the control group. In addition, no side effects were associated with the administration of the compound. All these in vitro results and the effective reduction of preneoplastic lesions in vivo suggest that styrylcoumarin 7-SC2 induces apoptosis in primary tumor cells and implies the potential ability at the early post-initiation phases of colon carcinogenesis. Moreover, hybrid 7-SC2 was docked to the three-dimensional structures of different apoptotic proteins and inflammatory cytokines, showing high binding affinities (ranging from −10.0 to −7.2 kcal/mol). Good correlation between calculated binding energies and experimental results was obtained. According to in silico ADME (absorption, distribution, metabolism, and excretion) studies of the 7-SC2, this novel compound has suitable drug-like properties, making it a potentially promising agent for therapy against colon cancer.
metadata.dc.identifier.eissn: 1554-8120
ISSN : 1054-2523
metadata.dc.identifier.doi: 10.1007/s00044-019-02487-2
Aparece en las colecciones: Artículos de Revista en Nutrición

Ficheros en este ítem:
Fichero Descripción Tamaño Formato  
MaldonadoMaria_2019_StyrylcoumarinInduces.pdfArtículo de investigación2.87 MBAdobe PDFVisualizar/Abrir

Este ítem está sujeto a una licencia Creative Commons Licencia Creative Commons Creative Commons