Antitumor role of histamine H4 receptor in human T-cell lymphoma. Therapeutic benefit for combination therapy with histamine and histone deacetylase inhibitors

MARIANGELES CLAUZURE; MONICA TAQUEZ DELGADO; LEANDRO CERCHIETTI; VANINA MEDINA

Congreso; LXIV Reunión Anual de la SAIC, Sociedad Argentina de Investigación Clínica; 2019

The discovery of the human histamine H4 receptor (H4R) has contributed to our understanding of histamine role in numerous physiological and pathological conditions, including tumor development and progression. High histamine levels have been determined in lymph nodes of patients with malignant lymphomas, but as far as we know there is no evidence of the expression and function of the H4R in this tumor type. The aims of this work were to study the expression of the H4R and to evaluate the therapeutic efficacy of histamine and H4R?s ligands as a single treatment or in combination with inhibitors of the histone deacetylase (HDACi) for the treatment of T-cell lymphoma (TCL). Results demonstrate the expression of H4R isoforms at the mRNA and protein levels in 3 human aggressive TCL cell lines (OCI-Ly12 and Karpas 299, Peripheral TCL; HuT78 Sezary Syndrome). HEK293T was used as a negative control. Histamine and specific H4R agonists (VUF8430 and JNJ28610244) significantly reduced cell viability (CellTiter-Blue Assay) in a dose-dependent manner and induced cell apoptosis (Caspase-Glo 3/7 Assay) in the three cell lines (p