Styrylcoumarin 7-SC2 induces apoptosis in SW480 human colon adenocarcinoma cells and inhibits azoxymethane-induced aberrant crypt foci formation in BALB/c mice

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-...

Full description

Autores:
Herrera Ramírez, Angie
Naranjo Preciado, Tonny Williams
Maldonado Celis, María Elena
Cardona Galeano, Wilson
Moreno Quintero, Gustavo Alberto
Yepes Pérez, Andrés Felipe
Tipo de recurso:
Article of investigation
Fecha de publicación:
2020
Institución:
Universidad de Antioquia
Repositorio:
Repositorio UdeA
Idioma:
eng
OAI Identifier:
oai:bibliotecadigital.udea.edu.co:10495/25331
Acceso en línea:
http://hdl.handle.net/10495/25331
Palabra clave:
Muerte Celular
Cell Death
Neoplasias Colorrectales
Colorectal Neoplasms
Styrylcoumarin
Rights
openAccess
License
http://creativecommons.org/licenses/by-nd/2.5/co/
id UDEA2_bfa08692994c690613e463ec36159182
oai_identifier_str oai:bibliotecadigital.udea.edu.co:10495/25331
network_acronym_str UDEA2
network_name_str Repositorio UdeA
repository_id_str
dc.title.spa.fl_str_mv Styrylcoumarin 7-SC2 induces apoptosis in SW480 human colon adenocarcinoma cells and inhibits azoxymethane-induced aberrant crypt foci formation in BALB/c mice
title Styrylcoumarin 7-SC2 induces apoptosis in SW480 human colon adenocarcinoma cells and inhibits azoxymethane-induced aberrant crypt foci formation in BALB/c mice
spellingShingle Styrylcoumarin 7-SC2 induces apoptosis in SW480 human colon adenocarcinoma cells and inhibits azoxymethane-induced aberrant crypt foci formation in BALB/c mice
Muerte Celular
Cell Death
Neoplasias Colorrectales
Colorectal Neoplasms
Styrylcoumarin
title_short Styrylcoumarin 7-SC2 induces apoptosis in SW480 human colon adenocarcinoma cells and inhibits azoxymethane-induced aberrant crypt foci formation in BALB/c mice
title_full Styrylcoumarin 7-SC2 induces apoptosis in SW480 human colon adenocarcinoma cells and inhibits azoxymethane-induced aberrant crypt foci formation in BALB/c mice
title_fullStr Styrylcoumarin 7-SC2 induces apoptosis in SW480 human colon adenocarcinoma cells and inhibits azoxymethane-induced aberrant crypt foci formation in BALB/c mice
title_full_unstemmed Styrylcoumarin 7-SC2 induces apoptosis in SW480 human colon adenocarcinoma cells and inhibits azoxymethane-induced aberrant crypt foci formation in BALB/c mice
title_sort Styrylcoumarin 7-SC2 induces apoptosis in SW480 human colon adenocarcinoma cells and inhibits azoxymethane-induced aberrant crypt foci formation in BALB/c mice
dc.creator.fl_str_mv Herrera Ramírez, Angie
Naranjo Preciado, Tonny Williams
Maldonado Celis, María Elena
Cardona Galeano, Wilson
Moreno Quintero, Gustavo Alberto
Yepes Pérez, Andrés Felipe
dc.contributor.author.none.fl_str_mv Herrera Ramírez, Angie
Naranjo Preciado, Tonny Williams
Maldonado Celis, María Elena
Cardona Galeano, Wilson
Moreno Quintero, Gustavo Alberto
Yepes Pérez, Andrés Felipe
dc.subject.decs.none.fl_str_mv Muerte Celular
Cell Death
Neoplasias Colorrectales
Colorectal Neoplasms
topic Muerte Celular
Cell Death
Neoplasias Colorrectales
Colorectal Neoplasms
Styrylcoumarin
dc.subject.proposal.spa.fl_str_mv Styrylcoumarin
description 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.
publishDate 2020
dc.date.issued.none.fl_str_mv 2020
dc.date.accessioned.none.fl_str_mv 2022-01-17T14:21:13Z
dc.date.available.none.fl_str_mv 2022-01-17T14:21:13Z
dc.type.spa.fl_str_mv info:eu-repo/semantics/article
dc.type.coarversion.fl_str_mv http://purl.org/coar/version/c_970fb48d4fbd8a85
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dc.type.local.spa.fl_str_mv Artículo de investigación
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dc.identifier.citation.spa.fl_str_mv 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)
dc.identifier.issn.none.fl_str_mv 1054-2523
dc.identifier.uri.none.fl_str_mv http://hdl.handle.net/10495/25331
dc.identifier.doi.none.fl_str_mv 10.1007/s00044-019-02487-2
dc.identifier.eissn.none.fl_str_mv 1554-8120
identifier_str_mv 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
url http://hdl.handle.net/10495/25331
dc.language.iso.spa.fl_str_mv eng
language eng
dc.relation.ispartofjournalabbrev.spa.fl_str_mv Med. Chem. Res.
dc.rights.spa.fl_str_mv info:eu-repo/semantics/openAccess
dc.rights.uri.*.fl_str_mv http://creativecommons.org/licenses/by-nd/2.5/co/
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eu_rights_str_mv openAccess
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dc.format.extent.spa.fl_str_mv 19
dc.format.mimetype.spa.fl_str_mv application/pdf
dc.publisher.spa.fl_str_mv Springer
dc.publisher.group.spa.fl_str_mv Impacto de Componentes Alimentarios en la Salud
Micología Médica y Experimental
Química de Plantas Colombianas
dc.publisher.place.spa.fl_str_mv Nueva York, Estados Unidos
institution Universidad de Antioquia
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spelling Herrera Ramírez, AngieNaranjo Preciado, Tonny WilliamsMaldonado Celis, María ElenaCardona Galeano, WilsonMoreno Quintero, Gustavo AlbertoYepes Pérez, Andrés Felipe2022-01-17T14:21:13Z2022-01-17T14:21:13Z2020Herrera-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)1054-2523http://hdl.handle.net/10495/2533110.1007/s00044-019-02487-21554-8120ABSTRACT: 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.COL0083811COL0013709COL001532919application/pdfengSpringerImpacto de Componentes Alimentarios en la SaludMicología Médica y ExperimentalQuímica de Plantas ColombianasNueva York, Estados Unidosinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_2df8fbb1https://purl.org/redcol/resource_type/ARTArtículo de investigaciónhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nd/2.5/co/http://purl.org/coar/access_right/c_abf2https://creativecommons.org/licenses/by-nc-sa/4.0/Styrylcoumarin 7-SC2 induces apoptosis in SW480 human colon adenocarcinoma cells and inhibits azoxymethane-induced aberrant crypt foci formation in BALB/c miceMuerte CelularCell DeathNeoplasias ColorrectalesColorectal NeoplasmsStyrylcoumarinMed. Chem. Res.Medicinal Chemistry Research377395293CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8817http://bibliotecadigital.udea.edu.co/bitstream/10495/25331/2/license_rdf9f7cf7f5e2fa6605483addd10a0d6ceeMD52LICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://bibliotecadigital.udea.edu.co/bitstream/10495/25331/3/license.txt8a4605be74aa9ea9d79846c1fba20a33MD53ORIGINALMaldonadoMaria_2019_StyrylcoumarinInduces.pdfMaldonadoMaria_2019_StyrylcoumarinInduces.pdfArtículo de investigaciónapplication/pdf2934820http://bibliotecadigital.udea.edu.co/bitstream/10495/25331/1/MaldonadoMaria_2019_StyrylcoumarinInduces.pdf48c370d5e627c7008507d4ff49e222b3MD5110495/25331oai:bibliotecadigital.udea.edu.co:10495/253312022-01-17 09:21:13.375Repositorio Institucional Universidad de Antioquiaandres.perez@udea.edu.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