Histamine H4 receptor agonism induces antitumor effects in human T-cell lymphoma
| Autor: | Mariángeles Clauzure, Mónica A. Táquez Delgado, Jude M. Phillip, Maria V. Revuelta, Leandro Cerchietti, Vanina A. Medina |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
panobinostat
QH301-705.5 proliferation Histamine Antagonists Antineoplastic Agents Apoptosis Lymphoma T-Cell Catalysis Cell Line Inorganic Chemistry Histamine Agonists Cell Line Tumor Humans H4R isoforms HISTAMINA Physical and Theoretical Chemistry Biology (General) T-cell lymphoma histamine apoptosis Molecular Biology QD1-999 Spectroscopy LINFOMA DE CÉLULAS T ISOFORMAS H4R Cell Proliferation Receptors Histamine H4 PANOBINOSTAT Organic Chemistry PROLIFERACION General Medicine Computer Science Applications APOPTOSIS Chemistry Oxidative Stress HEK293 Cells Histamine |
| Zdroj: | International Journal of Molecular Sciences Vol. 23, No.3, 2022 Repositorio Institucional (UCA) Pontificia Universidad Católica Argentina instacron:UCA International Journal of Molecular Sciences; Volume 23; Issue 3; Pages: 1378 International Journal of Molecular Sciences, Vol 23, Iss 1378, p 1378 (2022) |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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