Journal
CANCER LETTERS
Volume 288, Issue 2, Pages 170-176Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2009.06.034
Keywords
Pituitary adenoma; Dopamine receptor; Somatostatin receptor; Cell proliferation; Apoptosis; Chimera
Categories
Funding
- PRIN [2006060982]
- Fondazione Ospedale Maggiore IRCCS, Milan
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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. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
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