Producción CyT
Congreso
Autoría
Monica Taquez Delgado
;
Melisa N Nicoud
;
Ignacio Ospital
;
MF Correa
;
GAB Fernandes
;
Diego Martinel Lamas
;
JPS Fernandes
;
MEDINA, VANINA ARACELI
Fecha
2022
Editorial y Lugar de Edición
-
Resumen
Información suministrada por el agente en
SIGEVA
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 recep...
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<0.01). These more potent allylpiperazine compounds at H3R also exhibited higher antiproliferative and proapoptotic effects than their corresponding methylpiperazine analogues LINS01009 and LINS1010, respectively. We conclude that the H3R is involved in the regulation of breast cancer cell growth and progression, offering novel therapeutic potentials for H3R antagonists.
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Palabras Clave
BREAST CANCERHISTAMINE H3 RECEPTORANTAGONISTS