The dopamine-somatostatin chimeric compound BIM-23A760 exerts antiproliferative and cytotoxic effects in human non-functioning pituitary tumors by activating ERK1/2 and p38 pathways

Erika Peverelli; Luca Olgiati; Marco Locatelli; Paolo Magni; Marco Faustini Fustini; Giorgio Frank; Giovanna Mantovani; Paolo Beck-Peccoz; Anna Spada; Andrea Lania

doi:10.1016/j.canlet.2009.06.034

The dopamine-somatostatin chimeric compound BIM-23A760 exerts antiproliferative and cytotoxic effects in human non-functioning pituitary tumors by activating ERK1/2 and p38 pathways

Cancer Lett. 2010 Feb 28;288(2):170-6. doi: 10.1016/j.canlet.2009.06.034. Epub 2009 Jul 19.

Authors

Erika Peverelli¹, Luca Olgiati, Marco Locatelli, Paolo Magni, Marco Faustini Fustini, Giorgio Frank, Giovanna Mantovani, Paolo Beck-Peccoz, Anna Spada, Andrea Lania

Affiliation

¹ Dept. of Medical Sciences, University of Milan, Fondazione IRCCS Ospedale Maggiore Policlinico, Milano, Italy.

PMID: 19619936
DOI: 10.1016/j.canlet.2009.06.034

Abstract

The study investigated the effects of the dopamine-somatostatin chimeric compound BIM-23A760 on cell proliferation and apoptosis in cultured cells from human non-functioning pituitary tumors (NFPTs). Both BIM-23A760 and the dopaminergic agonist BIM-53097 induced a significant inhibition of cell proliferation associated with increased p27 expression, together with a significant increase in caspase-3 activity. Conversely, null or marginal effects were elicited by somatostatin analogs. Moreover, BIM-23A760 and BIM-53097 induced ERK1/2 and p38 phosphorylation and the blockade of these pathways prevented both the antiproliferative and the pro-apoptotic effects of these drugs. In conclusions the chimeric compound BIM-23A760 is able to exert cytostatic and cytotoxic effects in NFPTs, these phenomena being mainly mediated by DR2D and involving ERK1/2 and p38 pathways activation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects*
Caspase 3 / metabolism
Cell Proliferation / drug effects*
Cyclin-Dependent Kinase Inhibitor p27
Dopamine / analogs & derivatives*
Dopamine / pharmacology
Dopamine Agonists / pharmacology
Enzyme Activation
Female
Humans
Intracellular Signaling Peptides and Proteins / metabolism
MAP Kinase Signaling System / drug effects*
Male
Middle Aged
Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
Mitogen-Activated Protein Kinase 3 / metabolism*
Phosphorylation
Pituitary Neoplasms / enzymology*
Pituitary Neoplasms / pathology
Protein Kinase Inhibitors / pharmacology
Receptors, Dopamine D2 / agonists
Receptors, Dopamine D2 / metabolism
Receptors, Somatostatin / drug effects
Receptors, Somatostatin / metabolism
Somatostatin / analogs & derivatives*
Somatostatin / pharmacology
Tumor Cells, Cultured
p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

Antineoplastic Agents
CDKN1B protein, human
Dopamine Agonists
Intracellular Signaling Peptides and Proteins
Protein Kinase Inhibitors
Receptors, Dopamine D2
Receptors, Somatostatin
Cyclin-Dependent Kinase Inhibitor p27
Somatostatin
Mitogen-Activated Protein Kinase 3
p38 Mitogen-Activated Protein Kinases
CASP3 protein, human
Caspase 3
TBR-760
Dopamine