info:eu-repo/semantics/article
Styrylcoumarin 7-SC2 induces apoptosis in SW480 human colon adenocarcinoma cells and inhibits azoxymethane-induced aberrant crypt foci formation in BALB/c mice
Registro en:
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)
1054-2523
10.1007/s00044-019-02487-2
1554-8120
Autor
Herrera Ramírez, Angie
Naranjo Preciado, Tonny Williams
Maldonado Celis, María Elena
Cardona Galeano, Wilson
Moreno Quintero, Gustavo Alberto
Yepes Pérez, Andrés Felipe
Institución
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. COL0083811 COL0013709 COL0015329