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

Mariángeles Clauzure, Mónica A. Táquez Delgado, Jude M. Phillip, Maria V. Revuelta, Leandro Cerchietti, Vanina A. Medina

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number1378
JournalInternational journal of molecular sciences
Volume23
Issue number3
DOIs
StatePublished - Feb 1 2022
Externally publishedYes

Keywords

  • Apoptosis
  • H4R isoforms
  • Histamine
  • Panobinostat
  • Proliferation
  • T-cell lymphoma

ASJC Scopus subject areas

  • Molecular Biology
  • Spectroscopy
  • Catalysis
  • Inorganic Chemistry
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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