ConBr lectin modulates MAPKs and Akt pathways and triggers autophagic glioma cell death by a mechanism dependent upon caspase-8 activation

Autores
Wolin, Ingrid A. V.; Heinrich, Isabella A.; Nascimento, Ana Paula M.; Welter, Priscilla G.; Sosa, Liliana del Valle; de Paul, Ana Lucia; Zanotto Filho, Alfeu; Nedel, Cláudia Beatriz; Lima, Lara Dias; Osterne, Vinicius Jose Silva; Pinto Junior, Vanir Reis; Nascimento, Kyria S.; Cavada, Benildo S.; Leal, Rodrigo B.
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Glioblastoma multiforme is the most aggressive type of glioma, with limited treatment and poor prognosis. Despite some advances over the last decade, validation of novel and selective antiglioma agents remains a challenge in clinical pharmacology. Prior studies have shown that leguminous lectins may exert various biological effects, including antitumor properties. Accordingly, this study aimed to evaluate the mechanisms underlying the antiglioma activity of ConBr, a lectin extracted from the Canavalia brasiliensis seeds. ConBr at lower concentrations inhibited C6 glioma cell migration while higher levels promoted cell death dependent upon carbohydrate recognition domain (CRD) structure. ConBr increased p38MAPK and JNK and decreased ERK1/2 and Akt phosphorylation. Moreover, ConBr inhibited mTORC1 phosphorylation associated with accumulation of autophagic markers, such as acidic vacuoles and LC3 cleavage. Inhibition of early steps of autophagy with 3-methyl-adenine (3-MA) partially protected whereas the later autophagy inhibitor Chloroquine (CQ) had no protective effect upon ConBr cytotoxicity. ConBr also augmented caspase-3 activation without affecting mitochondrial function. Noteworthy, the caspase-8 inhibitor IETF-fmk attenuated ConBr induced autophagy and C6 glioma cell death. Finally, ConBr did not show cytotoxicity against primary astrocytes, suggesting a selective antiglioma activity. In summary, our results indicate that ConBr requires functional CRD lectin domain to exert antiglioma activity, and its cytotoxicity is associated with MAPKs and Akt pathways modulation and autophagy- and caspase-8- dependent cell death.
Fil: Wolin, Ingrid A. V.. Universidade Federal de Santa Catarina; Brasil
Fil: Heinrich, Isabella A.. Universidade Federal de Santa Catarina; Brasil
Fil: Nascimento, Ana Paula M.. Universidade Federal de Santa Catarina; Brasil
Fil: Welter, Priscilla G.. Universidade Federal de Santa Catarina; Brasil
Fil: Sosa, Liliana del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina
Fil: de Paul, Ana Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina
Fil: Zanotto Filho, Alfeu. Universidade Federal de Santa Catarina; Brasil
Fil: Nedel, Cláudia Beatriz. Universidade Federal de Santa Catarina; Brasil
Fil: Lima, Lara Dias. Universidade Estadual do Ceará; Brasil
Fil: Osterne, Vinicius Jose Silva. Universidade Estadual do Ceará; Brasil
Fil: Pinto Junior, Vanir Reis. Universidade Estadual do Ceará; Brasil
Fil: Nascimento, Kyria S.. Universidade Estadual do Ceará; Brasil
Fil: Cavada, Benildo S.. Universidade Estadual do Ceará; Brasil
Fil: Leal, Rodrigo B.. Universidade Federal de Santa Catarina; Brasil
Materia
AKT/MTORC1
AUTOPHAGY
CELL SIGNALING
CONBR
GLIOMA
LECTIN
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/139153
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/139153
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling ConBr lectin modulates MAPKs and Akt pathways and triggers autophagic glioma cell death by a mechanism dependent upon caspase-8 activationWolin, Ingrid A. V.Heinrich, Isabella A.Nascimento, Ana Paula M.Welter, Priscilla G.Sosa, Liliana del Vallede Paul, Ana LuciaZanotto Filho, AlfeuNedel, Cláudia BeatrizLima, Lara DiasOsterne, Vinicius Jose SilvaPinto Junior, Vanir ReisNascimento, Kyria S.Cavada, Benildo S.Leal, Rodrigo B.AKT/MTORC1AUTOPHAGYCELL SIGNALINGCONBRGLIOMALECTINhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Glioblastoma multiforme is the most aggressive type of glioma, with limited treatment and poor prognosis. Despite some advances over the last decade, validation of novel and selective antiglioma agents remains a challenge in clinical pharmacology. Prior studies have shown that leguminous lectins may exert various biological effects, including antitumor properties. Accordingly, this study aimed to evaluate the mechanisms underlying the antiglioma activity of ConBr, a lectin extracted from the Canavalia brasiliensis seeds. ConBr at lower concentrations inhibited C6 glioma cell migration while higher levels promoted cell death dependent upon carbohydrate recognition domain (CRD) structure. ConBr increased p38MAPK and JNK and decreased ERK1/2 and Akt phosphorylation. Moreover, ConBr inhibited mTORC1 phosphorylation associated with accumulation of autophagic markers, such as acidic vacuoles and LC3 cleavage. Inhibition of early steps of autophagy with 3-methyl-adenine (3-MA) partially protected whereas the later autophagy inhibitor Chloroquine (CQ) had no protective effect upon ConBr cytotoxicity. ConBr also augmented caspase-3 activation without affecting mitochondrial function. Noteworthy, the caspase-8 inhibitor IETF-fmk attenuated ConBr induced autophagy and C6 glioma cell death. Finally, ConBr did not show cytotoxicity against primary astrocytes, suggesting a selective antiglioma activity. In summary, our results indicate that ConBr requires functional CRD lectin domain to exert antiglioma activity, and its cytotoxicity is associated with MAPKs and Akt pathways modulation and autophagy- and caspase-8- dependent cell death.Fil: Wolin, Ingrid A. V.. Universidade Federal de Santa Catarina; BrasilFil: Heinrich, Isabella A.. Universidade Federal de Santa Catarina; BrasilFil: Nascimento, Ana Paula M.. Universidade Federal de Santa Catarina; BrasilFil: Welter, Priscilla G.. Universidade Federal de Santa Catarina; BrasilFil: Sosa, Liliana del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: de Paul, Ana Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Zanotto Filho, Alfeu. Universidade Federal de Santa Catarina; BrasilFil: Nedel, Cláudia Beatriz. Universidade Federal de Santa Catarina; BrasilFil: Lima, Lara Dias. Universidade Estadual do Ceará; BrasilFil: Osterne, Vinicius Jose Silva. Universidade Estadual do Ceará; BrasilFil: Pinto Junior, Vanir Reis. Universidade Estadual do Ceará; BrasilFil: Nascimento, Kyria S.. Universidade Estadual do Ceará; BrasilFil: Cavada, Benildo S.. Universidade Estadual do Ceará; BrasilFil: Leal, Rodrigo B.. Universidade Federal de Santa Catarina; BrasilElsevier France-Editions Scientifiques Medicales Elsevier2021-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/139153Wolin, Ingrid A. V.; Heinrich, Isabella A.; Nascimento, Ana Paula M.; Welter, Priscilla G.; Sosa, Liliana del Valle; et al.; ConBr lectin modulates MAPKs and Akt pathways and triggers autophagic glioma cell death by a mechanism dependent upon caspase-8 activation; Elsevier France-Editions Scientifiques Medicales Elsevier; Biochimie; 180; 1-2021; 186-2040300-9084CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.biochi.2020.11.003info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0300908420302790info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:11:45Zoai:ri.conicet.gov.ar:11336/139153instacron: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:34982025-09-03 10:11:45.587CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv ConBr lectin modulates MAPKs and Akt pathways and triggers autophagic glioma cell death by a mechanism dependent upon caspase-8 activation
title ConBr lectin modulates MAPKs and Akt pathways and triggers autophagic glioma cell death by a mechanism dependent upon caspase-8 activation
spellingShingle ConBr lectin modulates MAPKs and Akt pathways and triggers autophagic glioma cell death by a mechanism dependent upon caspase-8 activation
Wolin, Ingrid A. V.
AKT/MTORC1
AUTOPHAGY
CELL SIGNALING
CONBR
GLIOMA
LECTIN
title_short ConBr lectin modulates MAPKs and Akt pathways and triggers autophagic glioma cell death by a mechanism dependent upon caspase-8 activation
title_full ConBr lectin modulates MAPKs and Akt pathways and triggers autophagic glioma cell death by a mechanism dependent upon caspase-8 activation
title_fullStr ConBr lectin modulates MAPKs and Akt pathways and triggers autophagic glioma cell death by a mechanism dependent upon caspase-8 activation
title_full_unstemmed ConBr lectin modulates MAPKs and Akt pathways and triggers autophagic glioma cell death by a mechanism dependent upon caspase-8 activation
title_sort ConBr lectin modulates MAPKs and Akt pathways and triggers autophagic glioma cell death by a mechanism dependent upon caspase-8 activation
dc.creator.none.fl_str_mv Wolin, Ingrid A. V.
Heinrich, Isabella A.
Nascimento, Ana Paula M.
Welter, Priscilla G.
Sosa, Liliana del Valle
de Paul, Ana Lucia
Zanotto Filho, Alfeu
Nedel, Cláudia Beatriz
Lima, Lara Dias
Osterne, Vinicius Jose Silva
Pinto Junior, Vanir Reis
Nascimento, Kyria S.
Cavada, Benildo S.
Leal, Rodrigo B.
author Wolin, Ingrid A. V.
author_facet Wolin, Ingrid A. V.
Heinrich, Isabella A.
Nascimento, Ana Paula M.
Welter, Priscilla G.
Sosa, Liliana del Valle
de Paul, Ana Lucia
Zanotto Filho, Alfeu
Nedel, Cláudia Beatriz
Lima, Lara Dias
Osterne, Vinicius Jose Silva
Pinto Junior, Vanir Reis
Nascimento, Kyria S.
Cavada, Benildo S.
Leal, Rodrigo B.
author_role author
author2 Heinrich, Isabella A.
Nascimento, Ana Paula M.
Welter, Priscilla G.
Sosa, Liliana del Valle
de Paul, Ana Lucia
Zanotto Filho, Alfeu
Nedel, Cláudia Beatriz
Lima, Lara Dias
Osterne, Vinicius Jose Silva
Pinto Junior, Vanir Reis
Nascimento, Kyria S.
Cavada, Benildo S.
Leal, Rodrigo B.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv AKT/MTORC1
AUTOPHAGY
CELL SIGNALING
CONBR
GLIOMA
LECTIN
topic AKT/MTORC1
AUTOPHAGY
CELL SIGNALING
CONBR
GLIOMA
LECTIN
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Glioblastoma multiforme is the most aggressive type of glioma, with limited treatment and poor prognosis. Despite some advances over the last decade, validation of novel and selective antiglioma agents remains a challenge in clinical pharmacology. Prior studies have shown that leguminous lectins may exert various biological effects, including antitumor properties. Accordingly, this study aimed to evaluate the mechanisms underlying the antiglioma activity of ConBr, a lectin extracted from the Canavalia brasiliensis seeds. ConBr at lower concentrations inhibited C6 glioma cell migration while higher levels promoted cell death dependent upon carbohydrate recognition domain (CRD) structure. ConBr increased p38MAPK and JNK and decreased ERK1/2 and Akt phosphorylation. Moreover, ConBr inhibited mTORC1 phosphorylation associated with accumulation of autophagic markers, such as acidic vacuoles and LC3 cleavage. Inhibition of early steps of autophagy with 3-methyl-adenine (3-MA) partially protected whereas the later autophagy inhibitor Chloroquine (CQ) had no protective effect upon ConBr cytotoxicity. ConBr also augmented caspase-3 activation without affecting mitochondrial function. Noteworthy, the caspase-8 inhibitor IETF-fmk attenuated ConBr induced autophagy and C6 glioma cell death. Finally, ConBr did not show cytotoxicity against primary astrocytes, suggesting a selective antiglioma activity. In summary, our results indicate that ConBr requires functional CRD lectin domain to exert antiglioma activity, and its cytotoxicity is associated with MAPKs and Akt pathways modulation and autophagy- and caspase-8- dependent cell death.
Fil: Wolin, Ingrid A. V.. Universidade Federal de Santa Catarina; Brasil
Fil: Heinrich, Isabella A.. Universidade Federal de Santa Catarina; Brasil
Fil: Nascimento, Ana Paula M.. Universidade Federal de Santa Catarina; Brasil
Fil: Welter, Priscilla G.. Universidade Federal de Santa Catarina; Brasil
Fil: Sosa, Liliana del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina
Fil: de Paul, Ana Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina
Fil: Zanotto Filho, Alfeu. Universidade Federal de Santa Catarina; Brasil
Fil: Nedel, Cláudia Beatriz. Universidade Federal de Santa Catarina; Brasil
Fil: Lima, Lara Dias. Universidade Estadual do Ceará; Brasil
Fil: Osterne, Vinicius Jose Silva. Universidade Estadual do Ceará; Brasil
Fil: Pinto Junior, Vanir Reis. Universidade Estadual do Ceará; Brasil
Fil: Nascimento, Kyria S.. Universidade Estadual do Ceará; Brasil
Fil: Cavada, Benildo S.. Universidade Estadual do Ceará; Brasil
Fil: Leal, Rodrigo B.. Universidade Federal de Santa Catarina; Brasil
description Glioblastoma multiforme is the most aggressive type of glioma, with limited treatment and poor prognosis. Despite some advances over the last decade, validation of novel and selective antiglioma agents remains a challenge in clinical pharmacology. Prior studies have shown that leguminous lectins may exert various biological effects, including antitumor properties. Accordingly, this study aimed to evaluate the mechanisms underlying the antiglioma activity of ConBr, a lectin extracted from the Canavalia brasiliensis seeds. ConBr at lower concentrations inhibited C6 glioma cell migration while higher levels promoted cell death dependent upon carbohydrate recognition domain (CRD) structure. ConBr increased p38MAPK and JNK and decreased ERK1/2 and Akt phosphorylation. Moreover, ConBr inhibited mTORC1 phosphorylation associated with accumulation of autophagic markers, such as acidic vacuoles and LC3 cleavage. Inhibition of early steps of autophagy with 3-methyl-adenine (3-MA) partially protected whereas the later autophagy inhibitor Chloroquine (CQ) had no protective effect upon ConBr cytotoxicity. ConBr also augmented caspase-3 activation without affecting mitochondrial function. Noteworthy, the caspase-8 inhibitor IETF-fmk attenuated ConBr induced autophagy and C6 glioma cell death. Finally, ConBr did not show cytotoxicity against primary astrocytes, suggesting a selective antiglioma activity. In summary, our results indicate that ConBr requires functional CRD lectin domain to exert antiglioma activity, and its cytotoxicity is associated with MAPKs and Akt pathways modulation and autophagy- and caspase-8- dependent cell death.
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/11336/139153
Wolin, Ingrid A. V.; Heinrich, Isabella A.; Nascimento, Ana Paula M.; Welter, Priscilla G.; Sosa, Liliana del Valle; et al.; ConBr lectin modulates MAPKs and Akt pathways and triggers autophagic glioma cell death by a mechanism dependent upon caspase-8 activation; Elsevier France-Editions Scientifiques Medicales Elsevier; Biochimie; 180; 1-2021; 186-204
0300-9084
CONICET Digital
CONICET
url http://hdl.handle.net/11336/139153
identifier_str_mv Wolin, Ingrid A. V.; Heinrich, Isabella A.; Nascimento, Ana Paula M.; Welter, Priscilla G.; Sosa, Liliana del Valle; et al.; ConBr lectin modulates MAPKs and Akt pathways and triggers autophagic glioma cell death by a mechanism dependent upon caspase-8 activation; Elsevier France-Editions Scientifiques Medicales Elsevier; Biochimie; 180; 1-2021; 186-204
0300-9084
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.biochi.2020.11.003
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0300908420302790
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier France-Editions Scientifiques Medicales Elsevier
publisher.none.fl_str_mv Elsevier France-Editions Scientifiques Medicales 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 13.13397

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