Downregulation of GLI1- dependent survival pathway underlies arachidonic acid antitumoral activity

Autores
Comba, Andrea; Pasqualini, María Eugenia; Vara Mesler, Mariana; Silva, Renata Alejandra; García Fernandez Barrera, M; Fernández Zapico, Martín; Eynard, Aldo
Año de publicación
2013
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
2p
Fil: Comba, Andrea. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud (INICSA); Argentina
Fil: Pasqualini, María Eugenia. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud (INICSA); Argentina
Fil: Vara Mesler, Mariana. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud (INICSA); Argentina
Fil: Silva, Renata Alejandra. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud (INICSA); Argentina
Fil: García Fernández Barrera, A. Mayo Clinic, Rochester, MN; USA
Fil: Fernández Zapico, Martin. Mayo Clinic, Rochester, MN; USA
Fil: Eynard, Aldo. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud (INICSA); Argentina
Numerous studies have demonstrated a role for essential fatty acids (ePUFAs) during tumor evelopment. However, the molecularmechanism underlying this phenomenon remains elusive. Here, we defined a novel molecular mechanism explaining the ePUFA arachidonic acid (AA) anti-tumoral activity. We used in vivo and invitro assays to determine the effect of AA in primary tumor volume, lung micro-metastasis and apoptosis (TUNEL and Caspase 3/7activation) as well as gene expression (qRT-PCR and WB) andtranscriptional activity (Luciferase and ChIP assays). We observed a significant reduction in tumor volume and micro-metastasis incidence in AA-injected animals compared to the control group.Moreover, we demonstrated an increased apoptosis level in AA treated group in vivo and in vitro. Analysis of the mechanism showed that the AA treatment decreases the expression of the anti-apoptotic molecules Bcl-2 and Bfl-1/A1 by down-regulating their promoter activity. Moreover we found that the AA silencing of the oncogenic transcription factor GLI1 is the underling mechanism controlling Bcl-2 and Bfl-1/A1 expression. Finally, we demonstrated that AAinduced apoptosis can be rescued by overexpressing GLI1 in cancer cells. These results define a novel mechanism used by ePUFAs to inhibit tumor growth and suggest the use of AA for the development of new therapeutic approaches.
Fil: Comba, Andrea. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud (INICSA); Argentina
Fil: Pasqualini, María Eugenia. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud (INICSA); Argentina
Fil: Vara Mesler, Mariana. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud (INICSA); Argentina
Fil: Silva, Renata Alejandra. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud (INICSA); Argentina
Fil: García Fernández Barrera, A. Mayo Clinic, Rochester, MN; USA
Fil: Fernández Zapico, Martin. Mayo Clinic, Rochester, MN; USA
Fil: Eynard, Aldo. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud (INICSA); Argentina
Otras Ciencias Médicas
Materia
Arachidonic acid
GLI 1
Tumor
Regulation
Nivel de accesibilidad
acceso abierto
Condiciones de uso
Repositorio
Repositorio Digital Universitario (UNC)
Institución
Universidad Nacional de Córdoba
OAI Identificador
oai:rdu.unc.edu.ar:11086/22358
Acceder
id RDUUNC_42616f0557cec6e9ba961c6e23dc17e9
oai_identifier_str oai:rdu.unc.edu.ar:11086/22358
network_acronym_str RDUUNC
repository_id_str 2572
network_name_str Repositorio Digital Universitario (UNC)
spelling Downregulation of GLI1- dependent survival pathway underlies arachidonic acid antitumoral activityComba, AndreaPasqualini, María EugeniaVara Mesler, MarianaSilva, Renata AlejandraGarcía Fernandez Barrera, MFernández Zapico, MartínEynard, AldoArachidonic acidGLI 1TumorRegulation2pFil: Comba, Andrea. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud (INICSA); ArgentinaFil: Pasqualini, María Eugenia. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud (INICSA); ArgentinaFil: Vara Mesler, Mariana. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud (INICSA); ArgentinaFil: Silva, Renata Alejandra. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud (INICSA); ArgentinaFil: García Fernández Barrera, A. Mayo Clinic, Rochester, MN; USAFil: Fernández Zapico, Martin. Mayo Clinic, Rochester, MN; USAFil: Eynard, Aldo. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud (INICSA); ArgentinaNumerous studies have demonstrated a role for essential fatty acids (ePUFAs) during tumor evelopment. However, the molecularmechanism underlying this phenomenon remains elusive. Here, we defined a novel molecular mechanism explaining the ePUFA arachidonic acid (AA) anti-tumoral activity. We used in vivo and invitro assays to determine the effect of AA in primary tumor volume, lung micro-metastasis and apoptosis (TUNEL and Caspase 3/7activation) as well as gene expression (qRT-PCR and WB) andtranscriptional activity (Luciferase and ChIP assays). We observed a significant reduction in tumor volume and micro-metastasis incidence in AA-injected animals compared to the control group.Moreover, we demonstrated an increased apoptosis level in AA treated group in vivo and in vitro. Analysis of the mechanism showed that the AA treatment decreases the expression of the anti-apoptotic molecules Bcl-2 and Bfl-1/A1 by down-regulating their promoter activity. Moreover we found that the AA silencing of the oncogenic transcription factor GLI1 is the underling mechanism controlling Bcl-2 and Bfl-1/A1 expression. Finally, we demonstrated that AAinduced apoptosis can be rescued by overexpressing GLI1 in cancer cells. These results define a novel mechanism used by ePUFAs to inhibit tumor growth and suggest the use of AA for the development of new therapeutic approaches.Fil: Comba, Andrea. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud (INICSA); ArgentinaFil: Pasqualini, María Eugenia. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud (INICSA); ArgentinaFil: Vara Mesler, Mariana. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud (INICSA); ArgentinaFil: Silva, Renata Alejandra. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud (INICSA); ArgentinaFil: García Fernández Barrera, A. Mayo Clinic, Rochester, MN; USAFil: Fernández Zapico, Martin. Mayo Clinic, Rochester, MN; USAFil: Eynard, Aldo. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud (INICSA); ArgentinaOtras Ciencias MédicasArgentine Society for biochemistry and molecular biology research2013info:eu-repo/semantics/conferenceObjectinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfhttp://hdl.handle.net/11086/22358eng11086/14404info:eu-repo/semantics/openAccessreponame:Repositorio Digital Universitario (UNC)instname:Universidad Nacional de Córdobainstacron:UNC2025-09-29T13:43:15Zoai:rdu.unc.edu.ar:11086/22358Institucionalhttps://rdu.unc.edu.ar/Universidad públicaNo correspondehttp://rdu.unc.edu.ar/oai/snrdoca.unc@gmail.comArgentinaNo correspondeNo correspondeNo correspondeopendoar:25722025-09-29 13:43:15.711Repositorio Digital Universitario (UNC) - Universidad Nacional de Córdobafalse
dc.title.none.fl_str_mv Downregulation of GLI1- dependent survival pathway underlies arachidonic acid antitumoral activity
title Downregulation of GLI1- dependent survival pathway underlies arachidonic acid antitumoral activity
spellingShingle Downregulation of GLI1- dependent survival pathway underlies arachidonic acid antitumoral activity
Comba, Andrea
Arachidonic acid
GLI 1
Tumor
Regulation
title_short Downregulation of GLI1- dependent survival pathway underlies arachidonic acid antitumoral activity
title_full Downregulation of GLI1- dependent survival pathway underlies arachidonic acid antitumoral activity
title_fullStr Downregulation of GLI1- dependent survival pathway underlies arachidonic acid antitumoral activity
title_full_unstemmed Downregulation of GLI1- dependent survival pathway underlies arachidonic acid antitumoral activity
title_sort Downregulation of GLI1- dependent survival pathway underlies arachidonic acid antitumoral activity
dc.creator.none.fl_str_mv Comba, Andrea
Pasqualini, María Eugenia
Vara Mesler, Mariana
Silva, Renata Alejandra
García Fernandez Barrera, M
Fernández Zapico, Martín
Eynard, Aldo
author Comba, Andrea
author_facet Comba, Andrea
Pasqualini, María Eugenia
Vara Mesler, Mariana
Silva, Renata Alejandra
García Fernandez Barrera, M
Fernández Zapico, Martín
Eynard, Aldo
author_role author
author2 Pasqualini, María Eugenia
Vara Mesler, Mariana
Silva, Renata Alejandra
García Fernandez Barrera, M
Fernández Zapico, Martín
Eynard, Aldo
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Arachidonic acid
GLI 1
Tumor
Regulation
topic Arachidonic acid
GLI 1
Tumor
Regulation
dc.description.none.fl_txt_mv 2p
Fil: Comba, Andrea. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud (INICSA); Argentina
Fil: Pasqualini, María Eugenia. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud (INICSA); Argentina
Fil: Vara Mesler, Mariana. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud (INICSA); Argentina
Fil: Silva, Renata Alejandra. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud (INICSA); Argentina
Fil: García Fernández Barrera, A. Mayo Clinic, Rochester, MN; USA
Fil: Fernández Zapico, Martin. Mayo Clinic, Rochester, MN; USA
Fil: Eynard, Aldo. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud (INICSA); Argentina
Numerous studies have demonstrated a role for essential fatty acids (ePUFAs) during tumor evelopment. However, the molecularmechanism underlying this phenomenon remains elusive. Here, we defined a novel molecular mechanism explaining the ePUFA arachidonic acid (AA) anti-tumoral activity. We used in vivo and invitro assays to determine the effect of AA in primary tumor volume, lung micro-metastasis and apoptosis (TUNEL and Caspase 3/7activation) as well as gene expression (qRT-PCR and WB) andtranscriptional activity (Luciferase and ChIP assays). We observed a significant reduction in tumor volume and micro-metastasis incidence in AA-injected animals compared to the control group.Moreover, we demonstrated an increased apoptosis level in AA treated group in vivo and in vitro. Analysis of the mechanism showed that the AA treatment decreases the expression of the anti-apoptotic molecules Bcl-2 and Bfl-1/A1 by down-regulating their promoter activity. Moreover we found that the AA silencing of the oncogenic transcription factor GLI1 is the underling mechanism controlling Bcl-2 and Bfl-1/A1 expression. Finally, we demonstrated that AAinduced apoptosis can be rescued by overexpressing GLI1 in cancer cells. These results define a novel mechanism used by ePUFAs to inhibit tumor growth and suggest the use of AA for the development of new therapeutic approaches.
Fil: Comba, Andrea. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud (INICSA); Argentina
Fil: Pasqualini, María Eugenia. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud (INICSA); Argentina
Fil: Vara Mesler, Mariana. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud (INICSA); Argentina
Fil: Silva, Renata Alejandra. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud (INICSA); Argentina
Fil: García Fernández Barrera, A. Mayo Clinic, Rochester, MN; USA
Fil: Fernández Zapico, Martin. Mayo Clinic, Rochester, MN; USA
Fil: Eynard, Aldo. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud (INICSA); Argentina
Otras Ciencias Médicas
description 2p
publishDate 2013
dc.date.none.fl_str_mv 2013
dc.type.none.fl_str_mv info:eu-repo/semantics/conferenceObject
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
format conferenceObject
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11086/22358
url http://hdl.handle.net/11086/22358
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 11086/14404
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Argentine Society for biochemistry and molecular biology research
publisher.none.fl_str_mv Argentine Society for biochemistry and molecular biology research
dc.source.none.fl_str_mv reponame:Repositorio Digital Universitario (UNC)
instname:Universidad Nacional de Córdoba
instacron:UNC
reponame_str Repositorio Digital Universitario (UNC)
collection Repositorio Digital Universitario (UNC)
instname_str Universidad Nacional de Córdoba
instacron_str UNC
institution UNC
repository.name.fl_str_mv Repositorio Digital Universitario (UNC) - Universidad Nacional de Córdoba
repository.mail.fl_str_mv oca.unc@gmail.com
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