Glucose 6-phosphate dehydrogenase inhibition sensitizes melanoma cells to metformin treatment

Autores
Arbe, María Florencia; Agnetti, Lucrecia; Breininger, Elizabeth; Glikin, Gerardo Claudio; Finocchiaro, Liliana Maria Elena; Villaverde, Marcela Solange
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Most cancer cells exacerbate the pentose phosphate pathway (PPP) to enhance biosynthetic precursors and antioxidant defenses. Metformin, which is used as a first-line oral drug for the treatment of type 2 diabetes, has been proposed to inhibit the malignant progression of different types of cancers. However, metformin has shown poor efficacy as single agent in several clinical trials. Thus, the aim of the present work was to investigate whether the pharmacological inhibition of G6PDH, the first and rate-limiting enzyme of the PPP, by 6-amino nicotinamide (6-AN) potentiates the antitumoral activity of metformin on different human melanoma cell lines. Our results showed that 6-AN has sensitizing properties to metformin cytotoxicity. The combination of metformin and 6-AN decreased glucose consumption and lactate production, altered the mitochondrial potential and redox balance, and thereby blocked melanoma cell progression, directing cells to apoptosis and necrosis. To our knowledge, this is the first study describing the effect of this combination. Future preclinical studies should be performed to reveal the biological relevance of this finding.
Fil: Arbe, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
Fil: Agnetti, Lucrecia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
Fil: Breininger, Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Unidad Ejecutora de Investigaciones en Producción Animal. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Unidad Ejecutora de Investigaciones en Producción Animal; Argentina
Fil: Glikin, Gerardo Claudio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
Fil: Finocchiaro, Liliana Maria Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
Fil: Villaverde, Marcela Solange. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
Materia
6-AMINONICOTINAMIDE (6-AN)
METFORMIN
NADPH
PENTOSE PHOSPHATE PATHWAY (PPP)
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:11336/116792
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/116792
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Glucose 6-phosphate dehydrogenase inhibition sensitizes melanoma cells to metformin treatmentArbe, María FlorenciaAgnetti, LucreciaBreininger, ElizabethGlikin, Gerardo ClaudioFinocchiaro, Liliana Maria ElenaVillaverde, Marcela Solange6-AMINONICOTINAMIDE (6-AN)METFORMINNADPHPENTOSE PHOSPHATE PATHWAY (PPP)https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Most cancer cells exacerbate the pentose phosphate pathway (PPP) to enhance biosynthetic precursors and antioxidant defenses. Metformin, which is used as a first-line oral drug for the treatment of type 2 diabetes, has been proposed to inhibit the malignant progression of different types of cancers. However, metformin has shown poor efficacy as single agent in several clinical trials. Thus, the aim of the present work was to investigate whether the pharmacological inhibition of G6PDH, the first and rate-limiting enzyme of the PPP, by 6-amino nicotinamide (6-AN) potentiates the antitumoral activity of metformin on different human melanoma cell lines. Our results showed that 6-AN has sensitizing properties to metformin cytotoxicity. The combination of metformin and 6-AN decreased glucose consumption and lactate production, altered the mitochondrial potential and redox balance, and thereby blocked melanoma cell progression, directing cells to apoptosis and necrosis. To our knowledge, this is the first study describing the effect of this combination. Future preclinical studies should be performed to reveal the biological relevance of this finding.Fil: Arbe, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Agnetti, Lucrecia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Breininger, Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Unidad Ejecutora de Investigaciones en Producción Animal. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Unidad Ejecutora de Investigaciones en Producción Animal; ArgentinaFil: Glikin, Gerardo Claudio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Finocchiaro, Liliana Maria Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Villaverde, Marcela Solange. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaNeoplasia Press2020-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/116792Arbe, María Florencia; Agnetti, Lucrecia; Breininger, Elizabeth; Glikin, Gerardo Claudio; Finocchiaro, Liliana Maria Elena; et al.; Glucose 6-phosphate dehydrogenase inhibition sensitizes melanoma cells to metformin treatment; Neoplasia Press; Translational Oncology; 13; 11; 11-2020; 1-111936-5233CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.tranon.2020.100842info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S193652332030334X?via%3Dihub#!info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:15:44Zoai:ri.conicet.gov.ar:11336/116792instacron: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 10:15:45.029CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Glucose 6-phosphate dehydrogenase inhibition sensitizes melanoma cells to metformin treatment
title Glucose 6-phosphate dehydrogenase inhibition sensitizes melanoma cells to metformin treatment
spellingShingle Glucose 6-phosphate dehydrogenase inhibition sensitizes melanoma cells to metformin treatment
Arbe, María Florencia
6-AMINONICOTINAMIDE (6-AN)
METFORMIN
NADPH
PENTOSE PHOSPHATE PATHWAY (PPP)
title_short Glucose 6-phosphate dehydrogenase inhibition sensitizes melanoma cells to metformin treatment
title_full Glucose 6-phosphate dehydrogenase inhibition sensitizes melanoma cells to metformin treatment
title_fullStr Glucose 6-phosphate dehydrogenase inhibition sensitizes melanoma cells to metformin treatment
title_full_unstemmed Glucose 6-phosphate dehydrogenase inhibition sensitizes melanoma cells to metformin treatment
title_sort Glucose 6-phosphate dehydrogenase inhibition sensitizes melanoma cells to metformin treatment
dc.creator.none.fl_str_mv Arbe, María Florencia
Agnetti, Lucrecia
Breininger, Elizabeth
Glikin, Gerardo Claudio
Finocchiaro, Liliana Maria Elena
Villaverde, Marcela Solange
author Arbe, María Florencia
author_facet Arbe, María Florencia
Agnetti, Lucrecia
Breininger, Elizabeth
Glikin, Gerardo Claudio
Finocchiaro, Liliana Maria Elena
Villaverde, Marcela Solange
author_role author
author2 Agnetti, Lucrecia
Breininger, Elizabeth
Glikin, Gerardo Claudio
Finocchiaro, Liliana Maria Elena
Villaverde, Marcela Solange
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv 6-AMINONICOTINAMIDE (6-AN)
METFORMIN
NADPH
PENTOSE PHOSPHATE PATHWAY (PPP)
topic 6-AMINONICOTINAMIDE (6-AN)
METFORMIN
NADPH
PENTOSE PHOSPHATE PATHWAY (PPP)
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Most cancer cells exacerbate the pentose phosphate pathway (PPP) to enhance biosynthetic precursors and antioxidant defenses. Metformin, which is used as a first-line oral drug for the treatment of type 2 diabetes, has been proposed to inhibit the malignant progression of different types of cancers. However, metformin has shown poor efficacy as single agent in several clinical trials. Thus, the aim of the present work was to investigate whether the pharmacological inhibition of G6PDH, the first and rate-limiting enzyme of the PPP, by 6-amino nicotinamide (6-AN) potentiates the antitumoral activity of metformin on different human melanoma cell lines. Our results showed that 6-AN has sensitizing properties to metformin cytotoxicity. The combination of metformin and 6-AN decreased glucose consumption and lactate production, altered the mitochondrial potential and redox balance, and thereby blocked melanoma cell progression, directing cells to apoptosis and necrosis. To our knowledge, this is the first study describing the effect of this combination. Future preclinical studies should be performed to reveal the biological relevance of this finding.
Fil: Arbe, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
Fil: Agnetti, Lucrecia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
Fil: Breininger, Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Unidad Ejecutora de Investigaciones en Producción Animal. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Unidad Ejecutora de Investigaciones en Producción Animal; Argentina
Fil: Glikin, Gerardo Claudio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
Fil: Finocchiaro, Liliana Maria Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
Fil: Villaverde, Marcela Solange. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
description Most cancer cells exacerbate the pentose phosphate pathway (PPP) to enhance biosynthetic precursors and antioxidant defenses. Metformin, which is used as a first-line oral drug for the treatment of type 2 diabetes, has been proposed to inhibit the malignant progression of different types of cancers. However, metformin has shown poor efficacy as single agent in several clinical trials. Thus, the aim of the present work was to investigate whether the pharmacological inhibition of G6PDH, the first and rate-limiting enzyme of the PPP, by 6-amino nicotinamide (6-AN) potentiates the antitumoral activity of metformin on different human melanoma cell lines. Our results showed that 6-AN has sensitizing properties to metformin cytotoxicity. The combination of metformin and 6-AN decreased glucose consumption and lactate production, altered the mitochondrial potential and redox balance, and thereby blocked melanoma cell progression, directing cells to apoptosis and necrosis. To our knowledge, this is the first study describing the effect of this combination. Future preclinical studies should be performed to reveal the biological relevance of this finding.
publishDate 2020
dc.date.none.fl_str_mv 2020-11
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/11336/116792
Arbe, María Florencia; Agnetti, Lucrecia; Breininger, Elizabeth; Glikin, Gerardo Claudio; Finocchiaro, Liliana Maria Elena; et al.; Glucose 6-phosphate dehydrogenase inhibition sensitizes melanoma cells to metformin treatment; Neoplasia Press; Translational Oncology; 13; 11; 11-2020; 1-11
1936-5233
CONICET Digital
CONICET
url http://hdl.handle.net/11336/116792
identifier_str_mv Arbe, María Florencia; Agnetti, Lucrecia; Breininger, Elizabeth; Glikin, Gerardo Claudio; Finocchiaro, Liliana Maria Elena; et al.; Glucose 6-phosphate dehydrogenase inhibition sensitizes melanoma cells to metformin treatment; Neoplasia Press; Translational Oncology; 13; 11; 11-2020; 1-11
1936-5233
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.tranon.2020.100842
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S193652332030334X?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 Neoplasia Press
publisher.none.fl_str_mv Neoplasia Press
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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