RT Journal Article
T1 A New Generation Somatostatin-Dopamine Analogue Exerts Potent Antitumoral Actions on Pituitary Neuroendocrine Tumor Cells.
A1 Vazquez-Borrego, Mari C
A1 L-Lopez, Fernando
A1 Galvez-Moreno, Maria A
A1 Fuentes-Fayos, Antonio C
A1 Venegas-Moreno, Eva
A1 Herrera-Martinez, Aura D
A1 Blanco-Acevedo, Cristóbal
A1 Solivera, Juan
A1 Landsman, Tanya
A1 Gahete, Manuel D
A1 Soto-Moreno, Alfonso
A1 Culler, Michael D
A1 Castaño, Justo P
A1 Luque, Raul M
K1 Chimeric compound
K1 Dopamine
K1 Pituitary neuroendocrine tumors
K1 Receptor
K1 Somatostatin
AB Pituitary neuroendocrine tumors (PitNETs) represent approximately 15% of all intracranial tumors and usually are associated with severe comorbidities. Unfortunately, a relevant number of patients do not respond to currently available pharmacological treatments, that is, somatostatin analogs (SSAs) or dopamine-agonists (DA). Thus, novel, chimeric somatostatin/dopamine compounds (dopastatins) that could improve medical treatment of PitNETs have been designed. This study aims to determine the direct therapeutic effects of a new-generation dopastatin, BIM-065, on primary cell cultures from different PitNETs subtypes. Thirty-one PitNET-derived cell cultures (9 corticotropinomas, 9 somatotropinomas, 11 nonfunctioning pituitary adenomas [NFPAs], and 2 prolactinomas), were treated with BIM-065, and key functional endpoints were assessed (cell viability, apoptosis, hormone secretion, expression levels of key genes, free cytosolic [Ca2+]i dynamics, etc.). AtT-20 cell line was used to evaluate signaling pathways in response to BIM-065. This chimeric compound decreased cell viability in all corticotropinomas and somatotropinomas tested, but not in NFPAs. BIM-065 reduced ACTH, GH, chromogranin-A and PRL secretion, and increased apoptosis in corticotropinomas, somatotropinomas, and NFPAs. These effects were possibly mediated through modulation of pivotal signaling cascades like [Ca2+]i kinetic and Akt- or ERK1/2-phosphorylation. Our results unveil a robust antitumoral effect in vitro of the novel chimeric compound BIM-065 on the main PitNET subtypes, inform on the mechanisms involved, and suggest that BIM-065 could be an efficacious therapeutic option to be considered in the treatment of PitNETs.
PB S. Karger
YR 2019
FD 2019-05-19
LK http://hdl.handle.net/10668/14215
UL http://hdl.handle.net/10668/14215
LA en
NO Vázquez-Borrego MC, L-López F, Gálvez-Moreno MA, Fuentes-Fayos AC, Venegas-Moreno E, Herrera-Martínez AD, et al. A New Generation Somatostatin-Dopamine Analogue Exerts Potent Antitumoral Actions on Pituitary Neuroendocrine Tumor Cells. Neuroendocrinology. 2020;110(1-2):70-82
DS RISalud
RD Apr 7, 2025