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

• Autores: Clauzure, Mariángeles; Táquez Delgado, Mónica Alejandra; Phillip, Jude M.; Revuelta, Maria V.; Cerchietti, Leandro; Medina, Vanina Araceli
• Año de publicación: 2022
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: International Journal of Molecular Sciences Vol. 23, No.3, 2022
• Materia: LINFOMA DE CÉLULAS T; PANOBINOSTAT; HISTAMINA; ISOFORMAS H4R; PROLIFERACION; APOPTOSIS
• Institución: Pontificia Universidad Católica Argentina

Fil: Clauzure, Mariángeles. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Biología Tumoral e Inflamación; Argentina
Fil: Clauzure, Mariángeles. Universidad Nacional de La Pampa. Facultad de Ciencias Veterinarias; Argentina
Fil: Táquez Delgado, Mónica Alejandra. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Biología Tumoral e Inflamación; Argentina
Fil: Phillip, Jude M. Weill Cornell Medicine. Department of Medicine. Hematology and Oncology Division; Estados Unidos
Fil: Revuelta, Maria V. Weill Cornell Medicine. Department of Medicine. Hematology and Oncology Division; Estados Unidos
Fil: Cerchietti, Leandro. Weill Cornell Medicine. Department of Medicine. Hematology and Oncology Division; Estados Unidos
Fil: Medina, Vanina A. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Biología Tumoral e Inflamación; Argentina
Fil: Medina, Vanina A. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Clauzure, Mariángeles. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
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.