Camp efflux inhibition by nsaids: drug repositioning for pdac treatment

Autores
Cerviño, Ramiro Héctor; Gomez, Natalia; Shayo, Carina Claudia; Davio, Carlos Alberto; Yaneff, Agustín
Año de publicación
2021
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
In a previous work, we validated the inhibition of MRP4-dependant cAMP extrusion process as a promising therapeutic strategy for Pancreatic Ductal Adenocarcinoma (PDAC). In view of the therapeutic challenge associated with PDAC, we set out to search and characterize approved drugs that inhibit cAMP transport with the goal of establishing a repositioning strategy. Based on the results of this screening, we selected the Non-steroidal anti-inflammatory drugs (NSAIDs) as an interesting pharmacological family to inquire for rational drug repositioning. NSAIDs have been tested in the past as co-adjuvants in the therapy of various types of cancer, in many cases with positive results. Although their effects that depend on cyclooxygenase-2 inhibition are well described, the effects that are independent of this inhibition are far for being clear. We hypothesize that MRP4 inhibition could be a missing link in the overall action on tumor progression of these compounds. In this work, we measure the intracellular cAMP response upon treatment with 13 different NSAIDs using a technique developed in our laboratory in which we use HEK-293T cells stably transfected with the EPAC-SH187 sensor. Ibuprofen, acetyilsalicylic acid, Naproxen, Indomethacin, Diclofenac, Dexketoprofen and Ketorolac have shown to increase intracellular cAMP concentrations upon treatment (p<0.01). The concomitant significant reduction of extracellular cAMP upon treatment with these NSAIDs was also measured using a Radio-Binding Protein assay (RBP), which confirmed cAMP transport inhibition as one of the mechanisms that triggers intracellular cAMP increment (p<0.05). On the other hand, Celecoxib, Acetaminophen, Dipyrone, Phenacetin, Meloxicam and Piroxicam failed to increase intracellular cAMP upon treatment. These emerging results, together with an exhaustive literature search will allow us to select our repositioning
Fil: Cerviño, Ramiro Héctor. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fil: Gomez, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fil: Shayo, Carina Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Davio, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fil: Yaneff, Agustín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
LXVI Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXIX Reunión Anual de la Sociedad Argentina de Inmunología; LIII Reunión Anual de la Asociación Argentina de Farmacología Experimental y XI Reunión Anual de la Asociación Argentina de Nanomedicinas
Argentina
Sociedad Argentina de Investigación Clínica
Sociedad Argentina de Inmunología
Asociación Argentina de Farmacología Experimental
Asociación Argentina de Nanomedicinas
Materia
ABCC4/MRP4
cAMP
PANCREATIC DUCTAL ADENOCARCINOMA
DRUG REPOSITIONING
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:11336/190007
Acceder
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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Camp efflux inhibition by nsaids: drug repositioning for pdac treatmentCerviño, Ramiro HéctorGomez, NataliaShayo, Carina ClaudiaDavio, Carlos AlbertoYaneff, AgustínABCC4/MRP4cAMPPANCREATIC DUCTAL ADENOCARCINOMADRUG REPOSITIONINGhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3In a previous work, we validated the inhibition of MRP4-dependant cAMP extrusion process as a promising therapeutic strategy for Pancreatic Ductal Adenocarcinoma (PDAC). In view of the therapeutic challenge associated with PDAC, we set out to search and characterize approved drugs that inhibit cAMP transport with the goal of establishing a repositioning strategy. Based on the results of this screening, we selected the Non-steroidal anti-inflammatory drugs (NSAIDs) as an interesting pharmacological family to inquire for rational drug repositioning. NSAIDs have been tested in the past as co-adjuvants in the therapy of various types of cancer, in many cases with positive results. Although their effects that depend on cyclooxygenase-2 inhibition are well described, the effects that are independent of this inhibition are far for being clear. We hypothesize that MRP4 inhibition could be a missing link in the overall action on tumor progression of these compounds. In this work, we measure the intracellular cAMP response upon treatment with 13 different NSAIDs using a technique developed in our laboratory in which we use HEK-293T cells stably transfected with the EPAC-SH187 sensor. Ibuprofen, acetyilsalicylic acid, Naproxen, Indomethacin, Diclofenac, Dexketoprofen and Ketorolac have shown to increase intracellular cAMP concentrations upon treatment (p<0.01). The concomitant significant reduction of extracellular cAMP upon treatment with these NSAIDs was also measured using a Radio-Binding Protein assay (RBP), which confirmed cAMP transport inhibition as one of the mechanisms that triggers intracellular cAMP increment (p<0.05). On the other hand, Celecoxib, Acetaminophen, Dipyrone, Phenacetin, Meloxicam and Piroxicam failed to increase intracellular cAMP upon treatment. These emerging results, together with an exhaustive literature search will allow us to select our repositioningFil: Cerviño, Ramiro Héctor. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Gomez, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Shayo, Carina Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Davio, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Yaneff, Agustín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaLXVI Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXIX Reunión Anual de la Sociedad Argentina de Inmunología; LIII Reunión Anual de la Asociación Argentina de Farmacología Experimental y XI Reunión Anual de la Asociación Argentina de NanomedicinasArgentinaSociedad Argentina de Investigación ClínicaSociedad Argentina de InmunologíaAsociación Argentina de Farmacología ExperimentalAsociación Argentina de NanomedicinasFundación Revista Medicina2021info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/190007Camp efflux inhibition by nsaids: drug repositioning for pdac treatment; LXVI Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXIX Reunión Anual de la Sociedad Argentina de Inmunología; LIII Reunión Anual de la Asociación Argentina de Farmacología Experimental y XI Reunión Anual de la Asociación Argentina de Nanomedicinas; Argentina; 2021; 1-11669-9106CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.reunionbiociencias.com.ar/wp-content/uploads/2021/11/Revista-Medicina-2021.pdfNacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:05:35Zoai:ri.conicet.gov.ar:11336/190007instacron: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:34982025-09-10 13:05:36.155CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Camp efflux inhibition by nsaids: drug repositioning for pdac treatment
title Camp efflux inhibition by nsaids: drug repositioning for pdac treatment
spellingShingle Camp efflux inhibition by nsaids: drug repositioning for pdac treatment
Cerviño, Ramiro Héctor
ABCC4/MRP4
cAMP
PANCREATIC DUCTAL ADENOCARCINOMA
DRUG REPOSITIONING
title_short Camp efflux inhibition by nsaids: drug repositioning for pdac treatment
title_full Camp efflux inhibition by nsaids: drug repositioning for pdac treatment
title_fullStr Camp efflux inhibition by nsaids: drug repositioning for pdac treatment
title_full_unstemmed Camp efflux inhibition by nsaids: drug repositioning for pdac treatment
title_sort Camp efflux inhibition by nsaids: drug repositioning for pdac treatment
dc.creator.none.fl_str_mv Cerviño, Ramiro Héctor
Gomez, Natalia
Shayo, Carina Claudia
Davio, Carlos Alberto
Yaneff, Agustín
author Cerviño, Ramiro Héctor
author_facet Cerviño, Ramiro Héctor
Gomez, Natalia
Shayo, Carina Claudia
Davio, Carlos Alberto
Yaneff, Agustín
author_role author
author2 Gomez, Natalia
Shayo, Carina Claudia
Davio, Carlos Alberto
Yaneff, Agustín
author2_role author
author
author
author
dc.subject.none.fl_str_mv ABCC4/MRP4
cAMP
PANCREATIC DUCTAL ADENOCARCINOMA
DRUG REPOSITIONING
topic ABCC4/MRP4
cAMP
PANCREATIC DUCTAL ADENOCARCINOMA
DRUG REPOSITIONING
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv In a previous work, we validated the inhibition of MRP4-dependant cAMP extrusion process as a promising therapeutic strategy for Pancreatic Ductal Adenocarcinoma (PDAC). In view of the therapeutic challenge associated with PDAC, we set out to search and characterize approved drugs that inhibit cAMP transport with the goal of establishing a repositioning strategy. Based on the results of this screening, we selected the Non-steroidal anti-inflammatory drugs (NSAIDs) as an interesting pharmacological family to inquire for rational drug repositioning. NSAIDs have been tested in the past as co-adjuvants in the therapy of various types of cancer, in many cases with positive results. Although their effects that depend on cyclooxygenase-2 inhibition are well described, the effects that are independent of this inhibition are far for being clear. We hypothesize that MRP4 inhibition could be a missing link in the overall action on tumor progression of these compounds. In this work, we measure the intracellular cAMP response upon treatment with 13 different NSAIDs using a technique developed in our laboratory in which we use HEK-293T cells stably transfected with the EPAC-SH187 sensor. Ibuprofen, acetyilsalicylic acid, Naproxen, Indomethacin, Diclofenac, Dexketoprofen and Ketorolac have shown to increase intracellular cAMP concentrations upon treatment (p<0.01). The concomitant significant reduction of extracellular cAMP upon treatment with these NSAIDs was also measured using a Radio-Binding Protein assay (RBP), which confirmed cAMP transport inhibition as one of the mechanisms that triggers intracellular cAMP increment (p<0.05). On the other hand, Celecoxib, Acetaminophen, Dipyrone, Phenacetin, Meloxicam and Piroxicam failed to increase intracellular cAMP upon treatment. These emerging results, together with an exhaustive literature search will allow us to select our repositioning
Fil: Cerviño, Ramiro Héctor. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fil: Gomez, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fil: Shayo, Carina Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Davio, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fil: Yaneff, Agustín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
LXVI Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXIX Reunión Anual de la Sociedad Argentina de Inmunología; LIII Reunión Anual de la Asociación Argentina de Farmacología Experimental y XI Reunión Anual de la Asociación Argentina de Nanomedicinas
Argentina
Sociedad Argentina de Investigación Clínica
Sociedad Argentina de Inmunología
Asociación Argentina de Farmacología Experimental
Asociación Argentina de Nanomedicinas
description In a previous work, we validated the inhibition of MRP4-dependant cAMP extrusion process as a promising therapeutic strategy for Pancreatic Ductal Adenocarcinoma (PDAC). In view of the therapeutic challenge associated with PDAC, we set out to search and characterize approved drugs that inhibit cAMP transport with the goal of establishing a repositioning strategy. Based on the results of this screening, we selected the Non-steroidal anti-inflammatory drugs (NSAIDs) as an interesting pharmacological family to inquire for rational drug repositioning. NSAIDs have been tested in the past as co-adjuvants in the therapy of various types of cancer, in many cases with positive results. Although their effects that depend on cyclooxygenase-2 inhibition are well described, the effects that are independent of this inhibition are far for being clear. We hypothesize that MRP4 inhibition could be a missing link in the overall action on tumor progression of these compounds. In this work, we measure the intracellular cAMP response upon treatment with 13 different NSAIDs using a technique developed in our laboratory in which we use HEK-293T cells stably transfected with the EPAC-SH187 sensor. Ibuprofen, acetyilsalicylic acid, Naproxen, Indomethacin, Diclofenac, Dexketoprofen and Ketorolac have shown to increase intracellular cAMP concentrations upon treatment (p<0.01). The concomitant significant reduction of extracellular cAMP upon treatment with these NSAIDs was also measured using a Radio-Binding Protein assay (RBP), which confirmed cAMP transport inhibition as one of the mechanisms that triggers intracellular cAMP increment (p<0.05). On the other hand, Celecoxib, Acetaminophen, Dipyrone, Phenacetin, Meloxicam and Piroxicam failed to increase intracellular cAMP upon treatment. These emerging results, together with an exhaustive literature search will allow us to select our repositioning
publishDate 2021
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Reunión
Journal
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/190007
Camp efflux inhibition by nsaids: drug repositioning for pdac treatment; LXVI Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXIX Reunión Anual de la Sociedad Argentina de Inmunología; LIII Reunión Anual de la Asociación Argentina de Farmacología Experimental y XI Reunión Anual de la Asociación Argentina de Nanomedicinas; Argentina; 2021; 1-1
1669-9106
CONICET Digital
CONICET
url http://hdl.handle.net/11336/190007
identifier_str_mv Camp efflux inhibition by nsaids: drug repositioning for pdac treatment; LXVI Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXIX Reunión Anual de la Sociedad Argentina de Inmunología; LIII Reunión Anual de la Asociación Argentina de Farmacología Experimental y XI Reunión Anual de la Asociación Argentina de Nanomedicinas; Argentina; 2021; 1-1
1669-9106
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.reunionbiociencias.com.ar/wp-content/uploads/2021/11/Revista-Medicina-2021.pdf
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
application/pdf
dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Fundación Revista Medicina
publisher.none.fl_str_mv Fundación Revista Medicina
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
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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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