Histamine H4 receptor agonism induces antitumor effects in human T-cell lymphoma

Abstract: 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 cont...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Clauzure, Mariángeles, Táquez Delgado, Mónica Alejandra, Phillip, Jude M., Revuelta, Maria V., Cerchietti, Leandro, Medina, Vanina Araceli
Formato: Artículo
Lenguaje:Inglés
Publicado: Multidisciplinary Digital Publishing Institute 2022
Materias:
LINFOMA DE CÉLULAS T
PANOBINOSTAT
HISTAMINA
ISOFORMAS H4R
PROLIFERACION
APOPTOSIS
Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/14022
Aporte de:
Repositorio Institucional de la Universidad Católica Argentina (UCA) de Universidad Católica Argentina
id I33-R139-123456789-14022
record_format dspace
institution Universidad Católica Argentina
institution_str I-33
repository_str R-139
collection Repositorio Institucional de la Universidad Católica Argentina (UCA)
language Inglés
topic LINFOMA DE CÉLULAS T
PANOBINOSTAT
HISTAMINA
ISOFORMAS H4R
PROLIFERACION
APOPTOSIS
spellingShingle LINFOMA DE CÉLULAS T
PANOBINOSTAT
HISTAMINA
ISOFORMAS H4R
PROLIFERACION
APOPTOSIS
Clauzure, Mariángeles
Táquez Delgado, Mónica Alejandra
Phillip, Jude M.
Revuelta, Maria V.
Cerchietti, Leandro
Medina, Vanina Araceli
Histamine H4 receptor agonism induces antitumor effects in human T-cell lymphoma
topic_facet LINFOMA DE CÉLULAS T
PANOBINOSTAT
HISTAMINA
ISOFORMAS H4R
PROLIFERACION
APOPTOSIS
description Abstract: 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.
format Artículo
author Clauzure, Mariángeles
Táquez Delgado, Mónica Alejandra
Phillip, Jude M.
Revuelta, Maria V.
Cerchietti, Leandro
Medina, Vanina Araceli
author_facet Clauzure, Mariángeles
Táquez Delgado, Mónica Alejandra
Phillip, Jude M.
Revuelta, Maria V.
Cerchietti, Leandro
Medina, Vanina Araceli
author_sort Clauzure, Mariángeles
title Histamine H4 receptor agonism induces antitumor effects in human 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
publisher Multidisciplinary Digital Publishing Institute
publishDate 2022
url https://repositorio.uca.edu.ar/handle/123456789/14022
work_keys_str_mv AT clauzuremariangeles histamineh4receptoragonisminducesantitumoreffectsinhumantcelllymphoma
AT taquezdelgadomonicaalejandra histamineh4receptoragonisminducesantitumoreffectsinhumantcelllymphoma
AT phillipjudem histamineh4receptoragonisminducesantitumoreffectsinhumantcelllymphoma
AT revueltamariav histamineh4receptoragonisminducesantitumoreffectsinhumantcelllymphoma
AT cerchiettileandro histamineh4receptoragonisminducesantitumoreffectsinhumantcelllymphoma
AT medinavaninaaraceli histamineh4receptoragonisminducesantitumoreffectsinhumantcelllymphoma
bdutipo_str Repositorios
_version_ 1764820523782504449

Ejemplares similares