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Article

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

1
Laboratory of Tumor Biology and Inflammation, Institute for Biomedical Research (BIOMED), School of Medical Sciences, Pontifical Catholic University of Argentina (UCA), National Scientific and Technical Research Council (CONICET), Buenos Aires 1107, Argentina
2
Faculty of Veterinary Science, National University of La Pampa (UNLPam), General Pico 6360, Argentina
3
Hematology and Oncology Division, Department of Medicine, Weill Cornell Medicine, New York, NY 10065, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Paul Chazot and Ilona Obara
Int. J. Mol. Sci. 2022, 23(3), 1378; https://doi.org/10.3390/ijms23031378
Received: 16 November 2021 / Revised: 9 December 2021 / Accepted: 16 January 2022 / Published: 26 January 2022
(This article belongs to the Special Issue Molecular Biology of Histamine Systems)
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. View Full-Text
Keywords: T-cell lymphoma; panobinostat; histamine; H4R isoforms; proliferation; apoptosis T-cell lymphoma; panobinostat; histamine; H4R isoforms; proliferation; apoptosis
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MDPI and ACS Style

Clauzure, M.; Táquez Delgado, M.A.; Phillip, J.M.; Revuelta, M.V.; Cerchietti, L.; Medina, V.A. Histamine H4 Receptor Agonism Induces Antitumor Effects in Human T-Cell Lymphoma. Int. J. Mol. Sci. 2022, 23, 1378. https://doi.org/10.3390/ijms23031378

AMA Style

Clauzure M, Táquez Delgado MA, Phillip JM, Revuelta MV, Cerchietti L, Medina VA. Histamine H4 Receptor Agonism Induces Antitumor Effects in Human T-Cell Lymphoma. International Journal of Molecular Sciences. 2022; 23(3):1378. https://doi.org/10.3390/ijms23031378

Chicago/Turabian Style

Clauzure, Mariángeles, Mónica A. Táquez Delgado, Jude M. Phillip, Maria V. Revuelta, Leandro Cerchietti, and Vanina A. Medina. 2022. "Histamine H4 Receptor Agonism Induces Antitumor Effects in Human T-Cell Lymphoma" International Journal of Molecular Sciences 23, no. 3: 1378. https://doi.org/10.3390/ijms23031378

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