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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)170-176
Number of pages7
JournalCancer Letters
Volume288
Issue number2
DOIs
Publication statusPublished - Feb 28 2010

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MAP Kinase Signaling System
Pituitary Neoplasms
Somatostatin
Dopamine
Cell Proliferation
Dopamine Agonists
Cytostatic Agents
Caspase 3
Cultured Cells
Phosphorylation
Apoptosis
BIM 23A760
Pharmaceutical Preparations

Keywords

  • Apoptosis
  • Cell proliferation
  • Chimera
  • Dopamine receptor
  • Pituitary adenoma
  • Somatostatin receptor

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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title = "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",
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.",
keywords = "Apoptosis, Cell proliferation, Chimera, Dopamine receptor, Pituitary adenoma, Somatostatin receptor",
author = "Erika Peverelli and Luca Olgiati and Marco Locatelli and Paolo Magni and Fustini, {Marco Faustini} and Giorgio Frank and Giovanna Mantovani and Paolo Beck-Peccoz and Anna Spada and Andrea Lania",
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journal = "Cancer Letters",
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T1 - 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

AU - Peverelli, Erika

AU - Olgiati, Luca

AU - Locatelli, Marco

AU - Magni, Paolo

AU - Fustini, Marco Faustini

AU - Frank, Giorgio

AU - Mantovani, Giovanna

AU - Beck-Peccoz, Paolo

AU - Spada, Anna

AU - Lania, Andrea

PY - 2010/2/28

Y1 - 2010/2/28

N2 - 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.

AB - 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.

KW - Apoptosis

KW - Cell proliferation

KW - Chimera

KW - Dopamine receptor

KW - Pituitary adenoma

KW - Somatostatin receptor

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