Histamine H4 Receptor Agonism Induces Antitumor Effects in Human T-Cell Lymphoma

Autores
Clauzure, Mariangeles; Táquez Delgado, Mónica Alejandra; Phillip, Jude M.; Revuelta, María Victoria; Cerchietti, Leandro; Medina, Vanina Araceli
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The discovery of the human histamine H4 receptor (H4R) has contributed to our understanding of the role of histamine in numerous physiological and pathological conditions, including tumor development and progression. The lymph nodes of patients with malignant lymphomas have shown to contain high levels of histamine, however, less is known regarding the expression and function of the H4R in T-cell lymphoma (TCL). In this work we demonstrate the expression of H4R isoforms (mRNA and protein) in three human aggressive TCL (OCI-Ly12, Karpas 299, and HuT78). Histamine and specific H4R agonists (VUF8430 and JNJ28610244) significantly reduced cell viability in a dose-dependent manner (p < 0.05). The combined treatment with the H4R antagonist (JNJ7777120, 10 µM) reversed the effects of the H4R ligands. Importantly, we screened a drug repurposing library of 433 FDA-approved compounds (1 µM) in combination with histamine (10 µM) in Hut78 cells. Histamine produced a favorable antitumor effect with 18 of these compounds, including the histone deacetylase inhibitor panobinostat. Apoptosis, proliferation, and oxidative stress studies confirmed the antitumoral effects of the combination. We conclude that the H4R is expressed in TCL, and it is involved in histamine-mediated responses.
Fil: Clauzure, Mariangeles. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; Argentina. Universidad Nacional de La Pampa; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Táquez Delgado, Mónica Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; Argentina
Fil: Phillip, Jude M.. Weill Cornell Medicine; Estados Unidos
Fil: Revuelta, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Weill Cornell Medicine; Estados Unidos
Fil: Cerchietti, Leandro. Weill Cornell Medicine; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Medina, Vanina Araceli. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Materia
APOPTOSIS
H4R ISOFORMS
HISTAMINE
PANOBINOSTAT
PROLIFERATION
T-CELL LYMPHOMA
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/188300
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/188300
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Histamine H4 Receptor Agonism Induces Antitumor Effects in Human T-Cell LymphomaClauzure, MariangelesTáquez Delgado, Mónica AlejandraPhillip, Jude M.Revuelta, María VictoriaCerchietti, LeandroMedina, Vanina AraceliAPOPTOSISH4R ISOFORMSHISTAMINEPANOBINOSTATPROLIFERATIONT-CELL LYMPHOMAhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3The discovery of the human histamine H4 receptor (H4R) has contributed to our understanding of the role of histamine in numerous physiological and pathological conditions, including tumor development and progression. The lymph nodes of patients with malignant lymphomas have shown to contain high levels of histamine, however, less is known regarding the expression and function of the H4R in T-cell lymphoma (TCL). In this work we demonstrate the expression of H4R isoforms (mRNA and protein) in three human aggressive TCL (OCI-Ly12, Karpas 299, and HuT78). Histamine and specific H4R agonists (VUF8430 and JNJ28610244) significantly reduced cell viability in a dose-dependent manner (p < 0.05). The combined treatment with the H4R antagonist (JNJ7777120, 10 µM) reversed the effects of the H4R ligands. Importantly, we screened a drug repurposing library of 433 FDA-approved compounds (1 µM) in combination with histamine (10 µM) in Hut78 cells. Histamine produced a favorable antitumor effect with 18 of these compounds, including the histone deacetylase inhibitor panobinostat. Apoptosis, proliferation, and oxidative stress studies confirmed the antitumoral effects of the combination. We conclude that the H4R is expressed in TCL, and it is involved in histamine-mediated responses.Fil: Clauzure, Mariangeles. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; Argentina. Universidad Nacional de La Pampa; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Táquez Delgado, Mónica Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; ArgentinaFil: Phillip, Jude M.. Weill Cornell Medicine; Estados UnidosFil: Revuelta, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Weill Cornell Medicine; Estados UnidosFil: Cerchietti, Leandro. Weill Cornell Medicine; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Medina, Vanina Araceli. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaMultidisciplinary Digital Publishing Institute2022-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/188300Clauzure, Mariangeles; Táquez Delgado, Mónica Alejandra; Phillip, Jude M.; Revuelta, María Victoria; Cerchietti, Leandro; et al.; Histamine H4 Receptor Agonism Induces Antitumor Effects in Human T-Cell Lymphoma; Multidisciplinary Digital Publishing Institute; International Journal of Molecular Sciences; 23; 3; 2-2022; 1-151661-65961422-0067CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3390/ijms23031378info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1422-0067/23/3/1378info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:49:03Zoai:ri.conicet.gov.ar:11336/188300instacron: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 14:49:04.084CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Histamine H4 Receptor Agonism Induces Antitumor Effects in Human T-Cell Lymphoma
title Histamine H4 Receptor Agonism Induces Antitumor Effects in Human T-Cell Lymphoma
spellingShingle Histamine H4 Receptor Agonism Induces Antitumor Effects in Human T-Cell Lymphoma
Clauzure, Mariangeles
APOPTOSIS
H4R ISOFORMS
HISTAMINE
PANOBINOSTAT
PROLIFERATION
T-CELL LYMPHOMA
title_short Histamine H4 Receptor Agonism Induces Antitumor Effects in Human T-Cell Lymphoma
title_full Histamine H4 Receptor Agonism Induces Antitumor Effects in Human T-Cell Lymphoma
title_fullStr Histamine H4 Receptor Agonism Induces Antitumor Effects in Human T-Cell Lymphoma
title_full_unstemmed Histamine H4 Receptor Agonism Induces Antitumor Effects in Human T-Cell Lymphoma
title_sort Histamine H4 Receptor Agonism Induces Antitumor Effects in Human T-Cell Lymphoma
dc.creator.none.fl_str_mv Clauzure, Mariangeles
Táquez Delgado, Mónica Alejandra
Phillip, Jude M.
Revuelta, María Victoria
Cerchietti, Leandro
Medina, Vanina Araceli
author Clauzure, Mariangeles
author_facet Clauzure, Mariangeles
Táquez Delgado, Mónica Alejandra
Phillip, Jude M.
Revuelta, María Victoria
Cerchietti, Leandro
Medina, Vanina Araceli
author_role author
author2 Táquez Delgado, Mónica Alejandra
Phillip, Jude M.
Revuelta, María Victoria
Cerchietti, Leandro
Medina, Vanina Araceli
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv APOPTOSIS
H4R ISOFORMS
HISTAMINE
PANOBINOSTAT
PROLIFERATION
T-CELL LYMPHOMA
topic APOPTOSIS
H4R ISOFORMS
HISTAMINE
PANOBINOSTAT
PROLIFERATION
T-CELL LYMPHOMA
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The discovery of the human histamine H4 receptor (H4R) has contributed to our understanding of the role of histamine in numerous physiological and pathological conditions, including tumor development and progression. The lymph nodes of patients with malignant lymphomas have shown to contain high levels of histamine, however, less is known regarding the expression and function of the H4R in T-cell lymphoma (TCL). In this work we demonstrate the expression of H4R isoforms (mRNA and protein) in three human aggressive TCL (OCI-Ly12, Karpas 299, and HuT78). Histamine and specific H4R agonists (VUF8430 and JNJ28610244) significantly reduced cell viability in a dose-dependent manner (p < 0.05). The combined treatment with the H4R antagonist (JNJ7777120, 10 µM) reversed the effects of the H4R ligands. Importantly, we screened a drug repurposing library of 433 FDA-approved compounds (1 µM) in combination with histamine (10 µM) in Hut78 cells. Histamine produced a favorable antitumor effect with 18 of these compounds, including the histone deacetylase inhibitor panobinostat. Apoptosis, proliferation, and oxidative stress studies confirmed the antitumoral effects of the combination. We conclude that the H4R is expressed in TCL, and it is involved in histamine-mediated responses.
Fil: Clauzure, Mariangeles. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; Argentina. Universidad Nacional de La Pampa; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Táquez Delgado, Mónica Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; Argentina
Fil: Phillip, Jude M.. Weill Cornell Medicine; Estados Unidos
Fil: Revuelta, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Weill Cornell Medicine; Estados Unidos
Fil: Cerchietti, Leandro. Weill Cornell Medicine; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Medina, Vanina Araceli. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
description The discovery of the human histamine H4 receptor (H4R) has contributed to our understanding of the role of histamine in numerous physiological and pathological conditions, including tumor development and progression. The lymph nodes of patients with malignant lymphomas have shown to contain high levels of histamine, however, less is known regarding the expression and function of the H4R in T-cell lymphoma (TCL). In this work we demonstrate the expression of H4R isoforms (mRNA and protein) in three human aggressive TCL (OCI-Ly12, Karpas 299, and HuT78). Histamine and specific H4R agonists (VUF8430 and JNJ28610244) significantly reduced cell viability in a dose-dependent manner (p < 0.05). The combined treatment with the H4R antagonist (JNJ7777120, 10 µM) reversed the effects of the H4R ligands. Importantly, we screened a drug repurposing library of 433 FDA-approved compounds (1 µM) in combination with histamine (10 µM) in Hut78 cells. Histamine produced a favorable antitumor effect with 18 of these compounds, including the histone deacetylase inhibitor panobinostat. Apoptosis, proliferation, and oxidative stress studies confirmed the antitumoral effects of the combination. We conclude that the H4R is expressed in TCL, and it is involved in histamine-mediated responses.
publishDate 2022
dc.date.none.fl_str_mv 2022-02
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/11336/188300
Clauzure, Mariangeles; Táquez Delgado, Mónica Alejandra; Phillip, Jude M.; Revuelta, María Victoria; Cerchietti, Leandro; et al.; Histamine H4 Receptor Agonism Induces Antitumor Effects in Human T-Cell Lymphoma; Multidisciplinary Digital Publishing Institute; International Journal of Molecular Sciences; 23; 3; 2-2022; 1-15
1661-6596
1422-0067
CONICET Digital
CONICET
url http://hdl.handle.net/11336/188300
identifier_str_mv Clauzure, Mariangeles; Táquez Delgado, Mónica Alejandra; Phillip, Jude M.; Revuelta, María Victoria; Cerchietti, Leandro; et al.; Histamine H4 Receptor Agonism Induces Antitumor Effects in Human T-Cell Lymphoma; Multidisciplinary Digital Publishing Institute; International Journal of Molecular Sciences; 23; 3; 2-2022; 1-15
1661-6596
1422-0067
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3390/ijms23031378
info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1422-0067/23/3/1378
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
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 13.221938

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