Aqueous extract of Andean berry (Vaccinium meridionale Swartz) promotes antiproliferative effect of 5–fluorouracil and leucovorin treatment with or without oxaliplatin and inhibits metastatic potential in colon adenocarcinoma cells

ABSTRACT: Objective: To determine the effect of the aqueous extract of Andean berry (Vaccinium meridionale Swartz) alone or in combination with 5–fluorouracil (5–FU), leucovorin (LEU), and oxaliplatin (OXA) on proliferation, adhesion, and metastatic potential in colon adenocarcinoma cell lines. Meth...

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Autores:
Zapata Londoño, María Bibiana
Lozano Casabianca, Gustavo Argenor
Maldonado Celis, María Elena
Arango Varela, Sandra Sulay
Landázuri, Patricia
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:10495/43390
Acceso en línea:
https://hdl.handle.net/10495/43390
Palabra clave:
Vaccinium
Neoplasias del Colon
Colonic Neoplasms
Metástasis de la Neoplasia
Neoplasm Metastasis
Fluorouracilo
Fluorouracil
Leucovorina
Leucovorin
Línea Celular Tumoral
Oxaliplatino
Oxaliplatin
Frutas
Fruit
Fenoles
Phenols
https://id.nlm.nih.gov/mesh/D029796
https://id.nlm.nih.gov/mesh/D003110
https://id.nlm.nih.gov/mesh/D009362
https://id.nlm.nih.gov/mesh/D005472
https://id.nlm.nih.gov/mesh/D002955
Cell Line, Tumor
https://id.nlm.nih.gov/mesh/D045744
https://id.nlm.nih.gov/mesh/D000077150
https://id.nlm.nih.gov/mesh/D005638
https://id.nlm.nih.gov/mesh/D010636
Rights
openAccess
License
http://creativecommons.org/licenses/by-nc-nd/2.5/co/
id UDEA2_6b6962a579d5ad5ce19a3555ef884a0c
oai_identifier_str oai:bibliotecadigital.udea.edu.co:10495/43390
network_acronym_str UDEA2
network_name_str Repositorio UdeA
repository_id_str
dc.title.spa.fl_str_mv Aqueous extract of Andean berry (Vaccinium meridionale Swartz) promotes antiproliferative effect of 5–fluorouracil and leucovorin treatment with or without oxaliplatin and inhibits metastatic potential in colon adenocarcinoma cells
dc.title.translated.spa.fl_str_mv El extracto acuoso de la baya andina (Vaccinium meridionale Swartz) promueve el efecto antiproliferativo del tratamiento con 5–fluorouracilo y leucovorina con o sin oxaliplatino, en las células SW480 y SW620 e inhibe el potencial metastásico de células de adenocarcinoma de colon
title Aqueous extract of Andean berry (Vaccinium meridionale Swartz) promotes antiproliferative effect of 5–fluorouracil and leucovorin treatment with or without oxaliplatin and inhibits metastatic potential in colon adenocarcinoma cells
spellingShingle Aqueous extract of Andean berry (Vaccinium meridionale Swartz) promotes antiproliferative effect of 5–fluorouracil and leucovorin treatment with or without oxaliplatin and inhibits metastatic potential in colon adenocarcinoma cells
Vaccinium
Neoplasias del Colon
Colonic Neoplasms
Metástasis de la Neoplasia
Neoplasm Metastasis
Fluorouracilo
Fluorouracil
Leucovorina
Leucovorin
Línea Celular Tumoral
Oxaliplatino
Oxaliplatin
Frutas
Fruit
Fenoles
Phenols
https://id.nlm.nih.gov/mesh/D029796
https://id.nlm.nih.gov/mesh/D003110
https://id.nlm.nih.gov/mesh/D009362
https://id.nlm.nih.gov/mesh/D005472
https://id.nlm.nih.gov/mesh/D002955
Cell Line, Tumor
https://id.nlm.nih.gov/mesh/D045744
https://id.nlm.nih.gov/mesh/D000077150
https://id.nlm.nih.gov/mesh/D005638
https://id.nlm.nih.gov/mesh/D010636
title_short Aqueous extract of Andean berry (Vaccinium meridionale Swartz) promotes antiproliferative effect of 5–fluorouracil and leucovorin treatment with or without oxaliplatin and inhibits metastatic potential in colon adenocarcinoma cells
title_full Aqueous extract of Andean berry (Vaccinium meridionale Swartz) promotes antiproliferative effect of 5–fluorouracil and leucovorin treatment with or without oxaliplatin and inhibits metastatic potential in colon adenocarcinoma cells
title_fullStr Aqueous extract of Andean berry (Vaccinium meridionale Swartz) promotes antiproliferative effect of 5–fluorouracil and leucovorin treatment with or without oxaliplatin and inhibits metastatic potential in colon adenocarcinoma cells
title_full_unstemmed Aqueous extract of Andean berry (Vaccinium meridionale Swartz) promotes antiproliferative effect of 5–fluorouracil and leucovorin treatment with or without oxaliplatin and inhibits metastatic potential in colon adenocarcinoma cells
title_sort Aqueous extract of Andean berry (Vaccinium meridionale Swartz) promotes antiproliferative effect of 5–fluorouracil and leucovorin treatment with or without oxaliplatin and inhibits metastatic potential in colon adenocarcinoma cells
dc.creator.fl_str_mv Zapata Londoño, María Bibiana
Lozano Casabianca, Gustavo Argenor
Maldonado Celis, María Elena
Arango Varela, Sandra Sulay
Landázuri, Patricia
dc.contributor.author.none.fl_str_mv Zapata Londoño, María Bibiana
Lozano Casabianca, Gustavo Argenor
Maldonado Celis, María Elena
Arango Varela, Sandra Sulay
Landázuri, Patricia
dc.contributor.researchgroup.spa.fl_str_mv Impacto de Componentes Alimentarios en la Salud
dc.subject.decs.none.fl_str_mv Vaccinium
Neoplasias del Colon
Colonic Neoplasms
Metástasis de la Neoplasia
Neoplasm Metastasis
Fluorouracilo
Fluorouracil
Leucovorina
Leucovorin
Línea Celular Tumoral
Oxaliplatino
Oxaliplatin
Frutas
Fruit
Fenoles
Phenols
topic Vaccinium
Neoplasias del Colon
Colonic Neoplasms
Metástasis de la Neoplasia
Neoplasm Metastasis
Fluorouracilo
Fluorouracil
Leucovorina
Leucovorin
Línea Celular Tumoral
Oxaliplatino
Oxaliplatin
Frutas
Fruit
Fenoles
Phenols
https://id.nlm.nih.gov/mesh/D029796
https://id.nlm.nih.gov/mesh/D003110
https://id.nlm.nih.gov/mesh/D009362
https://id.nlm.nih.gov/mesh/D005472
https://id.nlm.nih.gov/mesh/D002955
Cell Line, Tumor
https://id.nlm.nih.gov/mesh/D045744
https://id.nlm.nih.gov/mesh/D000077150
https://id.nlm.nih.gov/mesh/D005638
https://id.nlm.nih.gov/mesh/D010636
dc.subject.meshuri.none.fl_str_mv https://id.nlm.nih.gov/mesh/D029796
https://id.nlm.nih.gov/mesh/D003110
https://id.nlm.nih.gov/mesh/D009362
https://id.nlm.nih.gov/mesh/D005472
https://id.nlm.nih.gov/mesh/D002955
Cell Line, Tumor
https://id.nlm.nih.gov/mesh/D045744
https://id.nlm.nih.gov/mesh/D000077150
https://id.nlm.nih.gov/mesh/D005638
https://id.nlm.nih.gov/mesh/D010636
description ABSTRACT: Objective: To determine the effect of the aqueous extract of Andean berry (Vaccinium meridionale Swartz) alone or in combination with 5–fluorouracil (5–FU), leucovorin (LEU), and oxaliplatin (OXA) on proliferation, adhesion, and metastatic potential in colon adenocarcinoma cell lines. Methods: Sulforhodamine B assay was used to evaluate cell viability, and crystal violet staining was employed to assess the adhesion and cloning efficiency of SW480 and SW620 cells. Commercial kits were used to evaluate the migration, invasion capacity, and levels of matrix metalloproteinases–2, –7, and –9 in the SW620 cell line. Results: The Andean berry extract (30% v/v) combined with the tested drugs showed a greater inhibitory effect on the viability of SW480 and SW620 cells than the drugs alone. The cloning efficiency of both cell lines was similar after treatment with drugs alone or combined with the extract. The extract decreased the adhesion of SW480 cells and also the migration and invasion of SW620 cells. Moreover, the drugs combined with the aqueous extract showed a greater inhibitory effect on the migration and invasion of SW620 cells than the drugs alone. The extract decreased the matrix metalloproteinase–9 (MMP–9) level of SW620 cells. Conclusions: The aqueous extract of Andean berry promoted the antiproliferative effect of the combination of 5–FU, LEU, and OXA in SW480 and SW620 cells while showing a potential antimetastatic effect in SW620 cells.
publishDate 2023
dc.date.issued.none.fl_str_mv 2023
dc.date.accessioned.none.fl_str_mv 2024-11-11T22:38:45Z
dc.date.available.none.fl_str_mv 2024-11-11T22:38:45Z
dc.type.spa.fl_str_mv Artículo de investigación
dc.type.coar.spa.fl_str_mv http://purl.org/coar/resource_type/c_2df8fbb1
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dc.identifier.citation.spa.fl_str_mv Zapata Londoño, M.B. et al. 2023. Aqueous extract of Andean berry (Vaccinium meridionale Swartz) promotes antiproliferative effect of 5-fluorouracil and leucovorin treatment with or without oxaliplatin and inhibits metastatic potential in colon adenocarcinoma cells. Revista Colombiana de Cancerología. 27, 4 (dic. 2023), 433–442.
dc.identifier.issn.none.fl_str_mv 0123-9015
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/10495/43390
dc.identifier.doi.none.fl_str_mv 10.35509/01239015.979
dc.identifier.eissn.none.fl_str_mv 2346-0199
identifier_str_mv Zapata Londoño, M.B. et al. 2023. Aqueous extract of Andean berry (Vaccinium meridionale Swartz) promotes antiproliferative effect of 5-fluorouracil and leucovorin treatment with or without oxaliplatin and inhibits metastatic potential in colon adenocarcinoma cells. Revista Colombiana de Cancerología. 27, 4 (dic. 2023), 433–442.
0123-9015
10.35509/01239015.979
2346-0199
url https://hdl.handle.net/10495/43390
dc.language.iso.spa.fl_str_mv eng
language eng
dc.relation.ispartofjournalabbrev.spa.fl_str_mv Rev. Colomb. Cancerol.
dc.relation.citationendpage.spa.fl_str_mv 442
dc.relation.citationissue.spa.fl_str_mv 4
dc.relation.citationstartpage.spa.fl_str_mv 433
dc.relation.citationvolume.spa.fl_str_mv 27
dc.relation.ispartofjournal.spa.fl_str_mv Revista Colombiana de Cancerología
dc.rights.uri.*.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/2.5/co/
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dc.format.extent.spa.fl_str_mv 10 páginas
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dc.publisher.spa.fl_str_mv Instituto Nacional de Cancerología
dc.publisher.place.spa.fl_str_mv Bogotá, Colombia
institution Universidad de Antioquia
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spelling Zapata Londoño, María BibianaLozano Casabianca, Gustavo ArgenorMaldonado Celis, María ElenaArango Varela, Sandra SulayLandázuri, PatriciaImpacto de Componentes Alimentarios en la Salud2024-11-11T22:38:45Z2024-11-11T22:38:45Z2023Zapata Londoño, M.B. et al. 2023. Aqueous extract of Andean berry (Vaccinium meridionale Swartz) promotes antiproliferative effect of 5-fluorouracil and leucovorin treatment with or without oxaliplatin and inhibits metastatic potential in colon adenocarcinoma cells. Revista Colombiana de Cancerología. 27, 4 (dic. 2023), 433–442.0123-9015https://hdl.handle.net/10495/4339010.35509/01239015.9792346-0199ABSTRACT: Objective: To determine the effect of the aqueous extract of Andean berry (Vaccinium meridionale Swartz) alone or in combination with 5–fluorouracil (5–FU), leucovorin (LEU), and oxaliplatin (OXA) on proliferation, adhesion, and metastatic potential in colon adenocarcinoma cell lines. Methods: Sulforhodamine B assay was used to evaluate cell viability, and crystal violet staining was employed to assess the adhesion and cloning efficiency of SW480 and SW620 cells. Commercial kits were used to evaluate the migration, invasion capacity, and levels of matrix metalloproteinases–2, –7, and –9 in the SW620 cell line. Results: The Andean berry extract (30% v/v) combined with the tested drugs showed a greater inhibitory effect on the viability of SW480 and SW620 cells than the drugs alone. The cloning efficiency of both cell lines was similar after treatment with drugs alone or combined with the extract. The extract decreased the adhesion of SW480 cells and also the migration and invasion of SW620 cells. Moreover, the drugs combined with the aqueous extract showed a greater inhibitory effect on the migration and invasion of SW620 cells than the drugs alone. The extract decreased the matrix metalloproteinase–9 (MMP–9) level of SW620 cells. Conclusions: The aqueous extract of Andean berry promoted the antiproliferative effect of the combination of 5–FU, LEU, and OXA in SW480 and SW620 cells while showing a potential antimetastatic effect in SW620 cells.RESUMEN: Objetivo: Determinar el efecto de un extracto acuoso de la baya andina (Vaccinium meridionale Swartz) solo o en combinación con 5–fluorouracilo (5–FU), leucovorina y oxaliplatino sobre proliferación, adhesión y potencial metastásico de líneas celulares de adenocarcinoma de colon. Métodos: Se utilizaron el ensayo de sulforodamina B, para determinar la viabilidad celular, y la tinción con cristal violeta, para evaluar la adhesión y la eficiencia de clonación de las células SW480 y SW620. Se emplearon estuches comerciales para evaluar la habilidad de migración, invasión y los niveles de metaloproteinasas 2, 7 y 9 en la línea celular SW620. Resultados: El extracto de la baya andina (30 % v/v), combinado con los medicamentos evaluados, mostró un mayor efecto sobre la viabilidad de las células SW480 y SW620, en comparación con los medicamentos solos. La eficiencia de clonación de ambas líneas celulares fue similar después del tratamiento con los medicamentos o con la combinación de estos con el extracto. El tratamiento con el extracto disminuyó la adhesión de la línea celular SW480, así como también la migración, y la invasión de las células SW620. Adicionalmente, los medicamentos combinados con el extracto acuoso mostraron un mayor efecto inhibitorio sobre la migración e invasión de las células SW620, en comparación con los medicamentos solos. El extracto disminuyó los niveles de MMP–9 de las células SW620. Conclusiones: El extracto acuoso de baya andina, o agraz, promovió el efecto del 5–FU, oxaliplatino y leucovorina sobre la proliferación de las células SW480 y SW620, además mostró un potencial antimetastásico sobre las células SW620.Universidad de Antioquia. Vicerrectoría de investigación. Comité para el Desarrollo de la Investigación - CODIColombia. Ministerio de Ciencia, Tecnología e Innovación - MinCienciasColombia. Ministerio de Educación Nacional - MinEducaciónColombia. Ministerio de Comercio, Industria y Turismo - MinCITCOL008381110 páginasapplication/pdfengInstituto Nacional de CancerologíaBogotá, Colombiahttp://creativecommons.org/licenses/by-nc-nd/2.5/co/https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Aqueous extract of Andean berry (Vaccinium meridionale Swartz) promotes antiproliferative effect of 5–fluorouracil and leucovorin treatment with or without oxaliplatin and inhibits metastatic potential in colon adenocarcinoma cellsEl extracto acuoso de la baya andina (Vaccinium meridionale Swartz) promueve el efecto antiproliferativo del tratamiento con 5–fluorouracilo y leucovorina con o sin oxaliplatino, en las células SW480 y SW620 e inhibe el potencial metastásico de células de adenocarcinoma de colonArtículo de investigaciónhttp://purl.org/coar/resource_type/c_2df8fbb1https://purl.org/redcol/resource_type/ARThttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionVacciniumNeoplasias del ColonColonic NeoplasmsMetástasis de la NeoplasiaNeoplasm MetastasisFluorouraciloFluorouracilLeucovorinaLeucovorinLínea Celular TumoralOxaliplatinoOxaliplatinFrutasFruitFenolesPhenolshttps://id.nlm.nih.gov/mesh/D029796https://id.nlm.nih.gov/mesh/D003110https://id.nlm.nih.gov/mesh/D009362https://id.nlm.nih.gov/mesh/D005472https://id.nlm.nih.gov/mesh/D002955Cell Line, Tumorhttps://id.nlm.nih.gov/mesh/D045744https://id.nlm.nih.gov/mesh/D000077150https://id.nlm.nih.gov/mesh/D005638https://id.nlm.nih.gov/mesh/D010636Rev. Colomb. Cancerol.442443327Revista Colombiana de Cancerología00000001066114680000000403726245RoR:03bp5hc83RoR:03fd5ne08CODI 2020–2021iMinCiencias 58580MinCiencias FP44842–211–2018PublicationLICENSElicense.txtlicense.txttext/plain; charset=utf-81748https://bibliotecadigital.udea.edu.co/bitstreams/86c0c986-c1e0-4154-89f1-81ed5372cce0/download8a4605be74aa9ea9d79846c1fba20a33MD52falseAnonymousREADORIGINALZapataMaria_2023_Aqueous_Extract_Andean_Berry.pdfZapataMaria_2023_Aqueous_Extract_Andean_Berry.pdfArtículo de investigaciónapplication/pdf726499https://bibliotecadigital.udea.edu.co/bitstreams/5c2295d9-d6cb-4712-9212-7326476ea6c8/download66b8cc35802900bd8ca3a5848423f8abMD51trueAnonymousREADTEXTZapataMaria_2023_Aqueous_Extract_Andean_Berry.pdf.txtZapataMaria_2023_Aqueous_Extract_Andean_Berry.pdf.txtExtracted texttext/plain45197https://bibliotecadigital.udea.edu.co/bitstreams/97a7788d-2df0-4a45-85c3-5d80f288da6c/downloadb90eaa3bc50ae69c3aea571eb214bfbfMD53falseAnonymousREADTHUMBNAILZapataMaria_2023_Aqueous_Extract_Andean_Berry.pdf.jpgZapataMaria_2023_Aqueous_Extract_Andean_Berry.pdf.jpgGenerated Thumbnailimage/jpeg15859https://bibliotecadigital.udea.edu.co/bitstreams/9fdc7309-77df-4830-958d-f26afa41e0d5/download6212e4419d666da805f8c082fc9754fbMD54falseAnonymousREAD10495/43390oai:bibliotecadigital.udea.edu.co:10495/433902025-03-26 20:40:00.49http://creativecommons.org/licenses/by-nc-nd/2.5/co/open.accesshttps://bibliotecadigital.udea.edu.coRepositorio Institucional de la Universidad de Antioquiaaplicacionbibliotecadigitalbiblioteca@udea.edu.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