Antitumor role of histamine h4 receptor in human t-cell lymphoma: therapeutic benefit for combination therapy with histamine and histone deacetylase inhibitors

Autores
Clauzure, Mariangeles; Táquez Delgado, Mónica Alejandra; Cerchietti, Leandro; Medina, Vanina Araceli
Año de publicación
2019
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
The discovery of the human histamine H4 receptor (H4R) has contributed to our understanding of histamine role in numerous physiological and pathological conditions, including tumor development and progression. High histamine levels have been determined in lymph nodes of patients with malignant lymphomas, but as far as we know there is no evidence of the expression and function of the H4R in this tumor type. The aims of this work were to study the expression of the H4R and to evaluate the therapeutic efficacy of histamine and H4R?s ligands as a single treatment or in combination with inhibitors of the histone deacetylase (HDACi) for the treatment of T-cell lymphoma (TCL). Results demonstrate the expression of H4R isoforms at the mRNA and protein levels in 3 human aggressive TCL cell lines (OCI-Ly12 and Karpas 299, Peripheral TCL; HuT78 Sezary Syndrome). HEK293T was used as a negative control. Histamine and specific H4R agonists (VUF8430 and JNJ28610244) significantly reduced cell viability (CellTiter-Blue Assay) in a dose-dependent manner and induced cell apoptosis (Caspase-Glo 3/7 Assay) in the three cell lines (p<0.05, n=3 independent experiments performed in triplicates). The combined treatment with the H4R antagonist (JNJ7777120, 10 µM) reversed the effects of the H4R ligands (10 µM) on TCL. Importantly, we screened active compounds against TCL, evaluating a dug repurposing library of 384 FDA-approved compounds (1 μM) in combination with histamine (10 μM) in Hut78 cells. Histamine produced a synergistic antitumor effect, evaluated with a metabolic assay, with 18 of these compounds, including the HDACi panobinostat. Apoptosis, proliferation and oxidative stress studies confirmed the antitumoral effects of the combination. We conclude that H4R is expressed in TCL and it is involved in histamine-mediated responses. Histamine could be an attractive compound to be used as a single therapy or in combination with HDACi for the treatment of TCL.
Fil: Clauzure, Mariangeles. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
Fil: Táquez Delgado, Mónica Alejandra. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
Fil: Cerchietti, Leandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Cornell University; Estados Unidos
Fil: Medina, Vanina Araceli. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
Reunión Anual de Sociedades de Biociencia
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Asociación Argentina de Farmacología Experimental
Sociedad Argentina de Biología
Sociedad Argentina de Protozoología
Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Asociación Argentina de Nanomedicinas
The Histochemical Society
Materia
HISTAMINE
LYMPHOMA
T CELL
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:11336/162728
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/162728
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Antitumor role of histamine h4 receptor in human t-cell lymphoma: therapeutic benefit for combination therapy with histamine and histone deacetylase inhibitorsClauzure, MariangelesTáquez Delgado, Mónica AlejandraCerchietti, LeandroMedina, Vanina AraceliHISTAMINELYMPHOMAT CELLhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The discovery of the human histamine H4 receptor (H4R) has contributed to our understanding of histamine role in numerous physiological and pathological conditions, including tumor development and progression. High histamine levels have been determined in lymph nodes of patients with malignant lymphomas, but as far as we know there is no evidence of the expression and function of the H4R in this tumor type. The aims of this work were to study the expression of the H4R and to evaluate the therapeutic efficacy of histamine and H4R?s ligands as a single treatment or in combination with inhibitors of the histone deacetylase (HDACi) for the treatment of T-cell lymphoma (TCL). Results demonstrate the expression of H4R isoforms at the mRNA and protein levels in 3 human aggressive TCL cell lines (OCI-Ly12 and Karpas 299, Peripheral TCL; HuT78 Sezary Syndrome). HEK293T was used as a negative control. Histamine and specific H4R agonists (VUF8430 and JNJ28610244) significantly reduced cell viability (CellTiter-Blue Assay) in a dose-dependent manner and induced cell apoptosis (Caspase-Glo 3/7 Assay) in the three cell lines (p<0.05, n=3 independent experiments performed in triplicates). The combined treatment with the H4R antagonist (JNJ7777120, 10 µM) reversed the effects of the H4R ligands (10 µM) on TCL. Importantly, we screened active compounds against TCL, evaluating a dug repurposing library of 384 FDA-approved compounds (1 μM) in combination with histamine (10 μM) in Hut78 cells. Histamine produced a synergistic antitumor effect, evaluated with a metabolic assay, with 18 of these compounds, including the HDACi panobinostat. Apoptosis, proliferation and oxidative stress studies confirmed the antitumoral effects of the combination. We conclude that H4R is expressed in TCL and it is involved in histamine-mediated responses. Histamine could be an attractive compound to be used as a single therapy or in combination with HDACi for the treatment of TCL.Fil: Clauzure, Mariangeles. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Táquez Delgado, Mónica Alejandra. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Cerchietti, Leandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Cornell University; Estados UnidosFil: Medina, Vanina Araceli. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaReunión Anual de Sociedades de BiocienciaMar del PlataArgentinaSociedad Argentina de Investigación ClínicaAsociación Argentina de Farmacología ExperimentalSociedad Argentina de BiologíaSociedad Argentina de ProtozoologíaAsociación Argentina de Ciencia y Tecnología de Animales de LaboratorioAsociación Argentina de NanomedicinasThe Histochemical SocietyFundación Revista Medicina2019info: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/11336/162728Antitumor role of histamine h4 receptor in human t-cell lymphoma: therapeutic benefit for combination therapy with histamine and histone deacetylase inhibitors; Reunión Anual de Sociedades de Biociencia; Mar del Plata; Argentina; 2019; 188-1880025-76801669-9106CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.medicinabuenosaires.com/indices-de-2010-a-2019/Nacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:34:59Zoai:ri.conicet.gov.ar:11336/162728instacron: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:34982025-10-15 15:34:59.982CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Antitumor role of histamine h4 receptor in human t-cell lymphoma: therapeutic benefit for combination therapy with histamine and histone deacetylase inhibitors
title Antitumor role of histamine h4 receptor in human t-cell lymphoma: therapeutic benefit for combination therapy with histamine and histone deacetylase inhibitors
spellingShingle Antitumor role of histamine h4 receptor in human t-cell lymphoma: therapeutic benefit for combination therapy with histamine and histone deacetylase inhibitors
Clauzure, Mariangeles
HISTAMINE
LYMPHOMA
T CELL
title_short Antitumor role of histamine h4 receptor in human t-cell lymphoma: therapeutic benefit for combination therapy with histamine and histone deacetylase inhibitors
title_full Antitumor role of histamine h4 receptor in human t-cell lymphoma: therapeutic benefit for combination therapy with histamine and histone deacetylase inhibitors
title_fullStr Antitumor role of histamine h4 receptor in human t-cell lymphoma: therapeutic benefit for combination therapy with histamine and histone deacetylase inhibitors
title_full_unstemmed Antitumor role of histamine h4 receptor in human t-cell lymphoma: therapeutic benefit for combination therapy with histamine and histone deacetylase inhibitors
title_sort Antitumor role of histamine h4 receptor in human t-cell lymphoma: therapeutic benefit for combination therapy with histamine and histone deacetylase inhibitors
dc.creator.none.fl_str_mv Clauzure, Mariangeles
Táquez Delgado, Mónica Alejandra
Cerchietti, Leandro
Medina, Vanina Araceli
author Clauzure, Mariangeles
author_facet Clauzure, Mariangeles
Táquez Delgado, Mónica Alejandra
Cerchietti, Leandro
Medina, Vanina Araceli
author_role author
author2 Táquez Delgado, Mónica Alejandra
Cerchietti, Leandro
Medina, Vanina Araceli
author2_role author
author
author
dc.subject.none.fl_str_mv HISTAMINE
LYMPHOMA
T CELL
topic HISTAMINE
LYMPHOMA
T CELL
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The discovery of the human histamine H4 receptor (H4R) has contributed to our understanding of histamine role in numerous physiological and pathological conditions, including tumor development and progression. High histamine levels have been determined in lymph nodes of patients with malignant lymphomas, but as far as we know there is no evidence of the expression and function of the H4R in this tumor type. The aims of this work were to study the expression of the H4R and to evaluate the therapeutic efficacy of histamine and H4R?s ligands as a single treatment or in combination with inhibitors of the histone deacetylase (HDACi) for the treatment of T-cell lymphoma (TCL). Results demonstrate the expression of H4R isoforms at the mRNA and protein levels in 3 human aggressive TCL cell lines (OCI-Ly12 and Karpas 299, Peripheral TCL; HuT78 Sezary Syndrome). HEK293T was used as a negative control. Histamine and specific H4R agonists (VUF8430 and JNJ28610244) significantly reduced cell viability (CellTiter-Blue Assay) in a dose-dependent manner and induced cell apoptosis (Caspase-Glo 3/7 Assay) in the three cell lines (p<0.05, n=3 independent experiments performed in triplicates). The combined treatment with the H4R antagonist (JNJ7777120, 10 µM) reversed the effects of the H4R ligands (10 µM) on TCL. Importantly, we screened active compounds against TCL, evaluating a dug repurposing library of 384 FDA-approved compounds (1 μM) in combination with histamine (10 μM) in Hut78 cells. Histamine produced a synergistic antitumor effect, evaluated with a metabolic assay, with 18 of these compounds, including the HDACi panobinostat. Apoptosis, proliferation and oxidative stress studies confirmed the antitumoral effects of the combination. We conclude that H4R is expressed in TCL and it is involved in histamine-mediated responses. Histamine could be an attractive compound to be used as a single therapy or in combination with HDACi for the treatment of TCL.
Fil: Clauzure, Mariangeles. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
Fil: Táquez Delgado, Mónica Alejandra. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
Fil: Cerchietti, Leandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Cornell University; Estados Unidos
Fil: Medina, Vanina Araceli. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
Reunión Anual de Sociedades de Biociencia
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Asociación Argentina de Farmacología Experimental
Sociedad Argentina de Biología
Sociedad Argentina de Protozoología
Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Asociación Argentina de Nanomedicinas
The Histochemical Society
description The discovery of the human histamine H4 receptor (H4R) has contributed to our understanding of histamine role in numerous physiological and pathological conditions, including tumor development and progression. High histamine levels have been determined in lymph nodes of patients with malignant lymphomas, but as far as we know there is no evidence of the expression and function of the H4R in this tumor type. The aims of this work were to study the expression of the H4R and to evaluate the therapeutic efficacy of histamine and H4R?s ligands as a single treatment or in combination with inhibitors of the histone deacetylase (HDACi) for the treatment of T-cell lymphoma (TCL). Results demonstrate the expression of H4R isoforms at the mRNA and protein levels in 3 human aggressive TCL cell lines (OCI-Ly12 and Karpas 299, Peripheral TCL; HuT78 Sezary Syndrome). HEK293T was used as a negative control. Histamine and specific H4R agonists (VUF8430 and JNJ28610244) significantly reduced cell viability (CellTiter-Blue Assay) in a dose-dependent manner and induced cell apoptosis (Caspase-Glo 3/7 Assay) in the three cell lines (p<0.05, n=3 independent experiments performed in triplicates). The combined treatment with the H4R antagonist (JNJ7777120, 10 µM) reversed the effects of the H4R ligands (10 µM) on TCL. Importantly, we screened active compounds against TCL, evaluating a dug repurposing library of 384 FDA-approved compounds (1 μM) in combination with histamine (10 μM) in Hut78 cells. Histamine produced a synergistic antitumor effect, evaluated with a metabolic assay, with 18 of these compounds, including the HDACi panobinostat. Apoptosis, proliferation and oxidative stress studies confirmed the antitumoral effects of the combination. We conclude that H4R is expressed in TCL and it is involved in histamine-mediated responses. Histamine could be an attractive compound to be used as a single therapy or in combination with HDACi for the treatment of TCL.
publishDate 2019
dc.date.none.fl_str_mv 2019
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/11336/162728
Antitumor role of histamine h4 receptor in human t-cell lymphoma: therapeutic benefit for combination therapy with histamine and histone deacetylase inhibitors; Reunión Anual de Sociedades de Biociencia; Mar del Plata; Argentina; 2019; 188-188
0025-7680
1669-9106
CONICET Digital
CONICET
url http://hdl.handle.net/11336/162728
identifier_str_mv Antitumor role of histamine h4 receptor in human t-cell lymphoma: therapeutic benefit for combination therapy with histamine and histone deacetylase inhibitors; Reunión Anual de Sociedades de Biociencia; Mar del Plata; Argentina; 2019; 188-188
0025-7680
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.medicinabuenosaires.com/indices-de-2010-a-2019/
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)
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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