Hexameric procyanidins inhibit colorectal cancer cell growth through both redox and non-redox regulation of the epidermal growth factor signaling pathway

Autores
Daveri, Elena; Adamo, Ana María; Alfine, Eugenia; Zhu, Wei; Oteiza, Patricia Isabel
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Dietary proanthocyanidins (PAC) consumption is associated with a decreased risk for colorectal cancer (CRC). Dysregulation of the epidermal growth factor (EGF) receptor (EGFR) signaling pathway is frequent in human cancers, including CRC. We previously showed that hexameric PAC (Hex) exert anti-proliferative and pro-apoptotic actions in human CRC cells. This work investigated if Hex could exert anti-CRC effects through its capacity to regulate the EGFR pathway. In proliferating Caco-2 cells, Hex acted attenuating EGF-induced EGFR dimerization and NADPH oxidase-dependent phosphorylation at Tyr 1068, decreasing EGFR location at lipid rafts, and inhibiting the downstream activation of pro-proliferative and anti-apoptotic pathways, i.e. Raf/MEK/ERK1/2 and PI3K/Akt. Hex also promoted EGFR internalization both in the absence and presence of EGF. While Hex decreased EGFR phosphorylation at Tyr 1068, it increased EGFR Tyr 1045 phosphorylation. The latter provides a docking site for the ubiquitin ligase c-Cbl and promotes EGFR degradation by lysosomes. Importantly, Hex acted synergistically with the EGFR-targeted chemotherapeutic drug Erlotinib, both in their capacity to decrease EGFR phosphorylation and inhibit cell growth. Thus, dietary PAC could exert anti-CRC actions by modulating, through both redox- and non-redox-regulated mechanisms, the EGFR pro-oncogenic signaling pathway. Additionally, Hex could also potentiate the actions of EGFR-targeted drugs.
Fil: Daveri, Elena. University of California at Davis; Estados Unidos
Fil: Adamo, Ana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Alfine, Eugenia. University of California at Davis; Estados Unidos
Fil: Zhu, Wei. University of California at Davis; Estados Unidos
Fil: Oteiza, Patricia Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Materia
COLORECTAL CANCER
EPIDERMAL GROWTH FACTOR RECEPTOR
NADPH OXIDASE
PROANTHOCYANIDINS
REDOX REGULATION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/181213
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/181213
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Hexameric procyanidins inhibit colorectal cancer cell growth through both redox and non-redox regulation of the epidermal growth factor signaling pathwayDaveri, ElenaAdamo, Ana MaríaAlfine, EugeniaZhu, WeiOteiza, Patricia IsabelCOLORECTAL CANCEREPIDERMAL GROWTH FACTOR RECEPTORNADPH OXIDASEPROANTHOCYANIDINSREDOX REGULATIONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Dietary proanthocyanidins (PAC) consumption is associated with a decreased risk for colorectal cancer (CRC). Dysregulation of the epidermal growth factor (EGF) receptor (EGFR) signaling pathway is frequent in human cancers, including CRC. We previously showed that hexameric PAC (Hex) exert anti-proliferative and pro-apoptotic actions in human CRC cells. This work investigated if Hex could exert anti-CRC effects through its capacity to regulate the EGFR pathway. In proliferating Caco-2 cells, Hex acted attenuating EGF-induced EGFR dimerization and NADPH oxidase-dependent phosphorylation at Tyr 1068, decreasing EGFR location at lipid rafts, and inhibiting the downstream activation of pro-proliferative and anti-apoptotic pathways, i.e. Raf/MEK/ERK1/2 and PI3K/Akt. Hex also promoted EGFR internalization both in the absence and presence of EGF. While Hex decreased EGFR phosphorylation at Tyr 1068, it increased EGFR Tyr 1045 phosphorylation. The latter provides a docking site for the ubiquitin ligase c-Cbl and promotes EGFR degradation by lysosomes. Importantly, Hex acted synergistically with the EGFR-targeted chemotherapeutic drug Erlotinib, both in their capacity to decrease EGFR phosphorylation and inhibit cell growth. Thus, dietary PAC could exert anti-CRC actions by modulating, through both redox- and non-redox-regulated mechanisms, the EGFR pro-oncogenic signaling pathway. Additionally, Hex could also potentiate the actions of EGFR-targeted drugs.Fil: Daveri, Elena. University of California at Davis; Estados UnidosFil: Adamo, Ana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Alfine, Eugenia. University of California at Davis; Estados UnidosFil: Zhu, Wei. University of California at Davis; Estados UnidosFil: Oteiza, Patricia Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaElsevier2021-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/181213Daveri, Elena; Adamo, Ana María; Alfine, Eugenia; Zhu, Wei; Oteiza, Patricia Isabel; Hexameric procyanidins inhibit colorectal cancer cell growth through both redox and non-redox regulation of the epidermal growth factor signaling pathway; Elsevier; Redox Biology; 38; 1-2021; 1-112213-2317CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.redox.2020.101830info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S2213231720310351?via%3Dihubinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:22:50Zoai:ri.conicet.gov.ar:11336/181213instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:22:50.751CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Hexameric procyanidins inhibit colorectal cancer cell growth through both redox and non-redox regulation of the epidermal growth factor signaling pathway
title Hexameric procyanidins inhibit colorectal cancer cell growth through both redox and non-redox regulation of the epidermal growth factor signaling pathway
spellingShingle Hexameric procyanidins inhibit colorectal cancer cell growth through both redox and non-redox regulation of the epidermal growth factor signaling pathway
Daveri, Elena
COLORECTAL CANCER
EPIDERMAL GROWTH FACTOR RECEPTOR
NADPH OXIDASE
PROANTHOCYANIDINS
REDOX REGULATION
title_short Hexameric procyanidins inhibit colorectal cancer cell growth through both redox and non-redox regulation of the epidermal growth factor signaling pathway
title_full Hexameric procyanidins inhibit colorectal cancer cell growth through both redox and non-redox regulation of the epidermal growth factor signaling pathway
title_fullStr Hexameric procyanidins inhibit colorectal cancer cell growth through both redox and non-redox regulation of the epidermal growth factor signaling pathway
title_full_unstemmed Hexameric procyanidins inhibit colorectal cancer cell growth through both redox and non-redox regulation of the epidermal growth factor signaling pathway
title_sort Hexameric procyanidins inhibit colorectal cancer cell growth through both redox and non-redox regulation of the epidermal growth factor signaling pathway
dc.creator.none.fl_str_mv Daveri, Elena
Adamo, Ana María
Alfine, Eugenia
Zhu, Wei
Oteiza, Patricia Isabel
author Daveri, Elena
author_facet Daveri, Elena
Adamo, Ana María
Alfine, Eugenia
Zhu, Wei
Oteiza, Patricia Isabel
author_role author
author2 Adamo, Ana María
Alfine, Eugenia
Zhu, Wei
Oteiza, Patricia Isabel
author2_role author
author
author
author
dc.subject.none.fl_str_mv COLORECTAL CANCER
EPIDERMAL GROWTH FACTOR RECEPTOR
NADPH OXIDASE
PROANTHOCYANIDINS
REDOX REGULATION
topic COLORECTAL CANCER
EPIDERMAL GROWTH FACTOR RECEPTOR
NADPH OXIDASE
PROANTHOCYANIDINS
REDOX REGULATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Dietary proanthocyanidins (PAC) consumption is associated with a decreased risk for colorectal cancer (CRC). Dysregulation of the epidermal growth factor (EGF) receptor (EGFR) signaling pathway is frequent in human cancers, including CRC. We previously showed that hexameric PAC (Hex) exert anti-proliferative and pro-apoptotic actions in human CRC cells. This work investigated if Hex could exert anti-CRC effects through its capacity to regulate the EGFR pathway. In proliferating Caco-2 cells, Hex acted attenuating EGF-induced EGFR dimerization and NADPH oxidase-dependent phosphorylation at Tyr 1068, decreasing EGFR location at lipid rafts, and inhibiting the downstream activation of pro-proliferative and anti-apoptotic pathways, i.e. Raf/MEK/ERK1/2 and PI3K/Akt. Hex also promoted EGFR internalization both in the absence and presence of EGF. While Hex decreased EGFR phosphorylation at Tyr 1068, it increased EGFR Tyr 1045 phosphorylation. The latter provides a docking site for the ubiquitin ligase c-Cbl and promotes EGFR degradation by lysosomes. Importantly, Hex acted synergistically with the EGFR-targeted chemotherapeutic drug Erlotinib, both in their capacity to decrease EGFR phosphorylation and inhibit cell growth. Thus, dietary PAC could exert anti-CRC actions by modulating, through both redox- and non-redox-regulated mechanisms, the EGFR pro-oncogenic signaling pathway. Additionally, Hex could also potentiate the actions of EGFR-targeted drugs.
Fil: Daveri, Elena. University of California at Davis; Estados Unidos
Fil: Adamo, Ana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Alfine, Eugenia. University of California at Davis; Estados Unidos
Fil: Zhu, Wei. University of California at Davis; Estados Unidos
Fil: Oteiza, Patricia Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
description Dietary proanthocyanidins (PAC) consumption is associated with a decreased risk for colorectal cancer (CRC). Dysregulation of the epidermal growth factor (EGF) receptor (EGFR) signaling pathway is frequent in human cancers, including CRC. We previously showed that hexameric PAC (Hex) exert anti-proliferative and pro-apoptotic actions in human CRC cells. This work investigated if Hex could exert anti-CRC effects through its capacity to regulate the EGFR pathway. In proliferating Caco-2 cells, Hex acted attenuating EGF-induced EGFR dimerization and NADPH oxidase-dependent phosphorylation at Tyr 1068, decreasing EGFR location at lipid rafts, and inhibiting the downstream activation of pro-proliferative and anti-apoptotic pathways, i.e. Raf/MEK/ERK1/2 and PI3K/Akt. Hex also promoted EGFR internalization both in the absence and presence of EGF. While Hex decreased EGFR phosphorylation at Tyr 1068, it increased EGFR Tyr 1045 phosphorylation. The latter provides a docking site for the ubiquitin ligase c-Cbl and promotes EGFR degradation by lysosomes. Importantly, Hex acted synergistically with the EGFR-targeted chemotherapeutic drug Erlotinib, both in their capacity to decrease EGFR phosphorylation and inhibit cell growth. Thus, dietary PAC could exert anti-CRC actions by modulating, through both redox- and non-redox-regulated mechanisms, the EGFR pro-oncogenic signaling pathway. Additionally, Hex could also potentiate the actions of EGFR-targeted drugs.
publishDate 2021
dc.date.none.fl_str_mv 2021-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/181213
Daveri, Elena; Adamo, Ana María; Alfine, Eugenia; Zhu, Wei; Oteiza, Patricia Isabel; Hexameric procyanidins inhibit colorectal cancer cell growth through both redox and non-redox regulation of the epidermal growth factor signaling pathway; Elsevier; Redox Biology; 38; 1-2021; 1-11
2213-2317
CONICET Digital
CONICET
url http://hdl.handle.net/11336/181213
identifier_str_mv Daveri, Elena; Adamo, Ana María; Alfine, Eugenia; Zhu, Wei; Oteiza, Patricia Isabel; Hexameric procyanidins inhibit colorectal cancer cell growth through both redox and non-redox regulation of the epidermal growth factor signaling pathway; Elsevier; Redox Biology; 38; 1-2021; 1-11
2213-2317
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.redox.2020.101830
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S2213231720310351?via%3Dihub
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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