ANTITUMORAL PROPERTIES OF NOVEL HISTAMINE H3 RECEPTOR ANTAGONISTS FOR BREAST CANCER TREATMENT

TÁQUEZ DELGADO, MÓNICA A.; NICOUD, MELISA B; OSPITAL, IGNACIO A.; BORGES FERNANDES, GUSTAVO; CORREA, MICHELLE; MARTINEL LAMAS, D.J.; FERNANDES, JOAO; MEDINA, VANINA A

hannover

Congreso; European Histamine Research Society 50th Annual Meeting; 2022

EUROPEAN HISTAMINE RESEARCH SOCIETY

We have reported the expression of the histamine H3 receptor (H3R) in human benign and malignant lesions, and cell lines derived from human mammary glands. Its expression is highly correlated with proliferation in breast cancer specimens.In this work, we aimed at investigating the potential antitumoral activity of 4 novel H3R antagonists, 1-(2,3-dihydro-1-benzofuran-2-yl)methylpiperazines (LINS01 compounds), which showed high affinity for the human H3R and selectivity over other histamine receptors. Cell viability and proliferation were assessed by cell titer blue assay and colony formation in human MDA-MB-231 and murine 4T1 triple negative breast cancer cells. Cell apoptosis was assessed by Annexin V staining and flow cytometry together with TUNEL assay, while cell migration was evaluated by wound-healing assay and transwell system.Results indicate that compounds LINS01009, LINS01010, LINS01022 and LINS01023 (0.01-100 μM) produced a concentration-dependent inhibition on cell growth. The highest responses were observed for LINS01022 and LINS01023, showing an IC50 of 9.9±1.1 and 5.2±1.2 μM for MDA-MB-231 cells, and 11.1±1.3 and 3.4±1.2 μM for 4T1 cells, respectively, in the clonogenic assay. These effects were partially reversed by the selective H3R agonist (R)-alpha-methylhistamine.LINS01022 and LINS01023 (25-50 μM) induced cell apoptosis (3 to 7-fold-increase) and suppressed cell migration in both cell lines (ANOVA, P