Producción CyT
Congreso
Autoría
Ospital, Ignacio A.
;
Táquez Delgado, Mónica A.
;
NICOUD, MELISA BEATRIZ
;
Correa, Michelle
;
Borges Fernandes, Gustavo
;
Andrade, Isabela W.
;
Lauretta, Paolo
;
Martínez Vivot, Rocío
;
Comba, María Betina
;
Zanardi, María Marta
;
Speisky, Daniela
;
Uriburu, Juan L.
;
Fernandes, Joao
;
Medina, V.A.
Fecha
2023
Editorial y Lugar de Edición
Fundación revista medicina
ISSN
0025-7680
Resumen
Información suministrada por el agente en
SIGEVA
Lung cancer is the leading cause of cancer-related deaths worldwide, accounting for the highest mortality rates among both men and women. The most common type of lung cancer is non-small cell carcinoma (NSCLC) and comprises squamous cell carcinoma and adenocarcinoma. The latter is the most common subtype and despite significant advances in therapeutics, the survival of most patients remains abysmal. It was previously reported that the expression levels of H3R were significantly increased in NSC...
Lung cancer is the leading cause of cancer-related deaths worldwide, accounting for the highest mortality rates among both men and women. The most common type of lung cancer is non-small cell carcinoma (NSCLC) and comprises squamous cell carcinoma and adenocarcinoma. The latter is the most common subtype and despite significant advances in therapeutics, the survival of most patients remains abysmal. It was previously reported that the expression levels of H3R were significantly increased in NSCLC samples, and high levels of H3R were associated with poor overall survival in NSCLC patients. The H3R antagonist ciproxifan inhibited cell proliferation and epithelial to mesenchymal progression in lung adenocarcinoma cells.The aims of this work were to evaluate the expression of H3R in lung cancer cell lines and to investigate the antitumoral properties of novel H3R antagonists, 1-(2,3-dihydro-1-benzofuran-2-yl)methylpiperazines (LINS01 compounds). Cell viability, clonogenic proliferation, cell apoptosis (Annexin-V and TUNEL) and migration (wound-healing assay and transwell system) were assessed in human A549 adenocarcinona and H596 adenosquamous carcinoma cells. Results indicate that A549 and H596 cells show H3R protein expression. Treatment of lung cancer cells with LINS01009, LINS01010, LINS01016, LINS01022 and LINS01023 compounds (0.001-50 μM) produced a significant concentration-dependent inhibition on cell growth, increasing cell apoptosis (P<0.01). The most potent responses were observed with LINS01016, LINS01022, LINS01023, showing a half-maximal inhibitory concentration (IC50) of 7.9±1.2, 2.7±1.2 and 0.9±0.8 μM for A549 cells in the clonogenic assay. These compounds also produced cytotoxic effects on H596 cells, although to a lesser extent. These most potent compounds also exhibited the highest affinity constant at the H3R. We conclude that H3R could be a novel target for lung cancer treatment, offering therapeutic potentials for selective H3R antagonists.
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Palabras Clave
BREAST CANCERMETHYL PIPERAZINESRH3 RECEPTOR