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- Title
The Novel Somatostatin Receptor 2/Dopamine Type 2 Receptor Chimeric Compound BIM-23A758 Decreases the Viability of Human GOT1 Midgut Carcinoid Cells.
- Authors
Zitzmann, Kathrin; andersen, Sandra; Vlotides, George; Spöttl, Gerald; Zhang, Shengwen; Datta, Rakesh; Culler, Michael; Göke, Burkhard; auernhammer, Christoph J.
- Abstract
The majority of neuroendocrine tumors (NETs) of the gastroenteropancreatic system coexpress somatostatin receptors (SSTRs) and dopamine type 2 receptors (D2R), thus providing a rationale for the use of novel SSTR2/D2R chimeric compounds in NET disease. Here we investigate the antitumor potential of the SSTR2/D2R chimeric compounds BIM-23A760 and BIM-23A758 in comparison to the selective SSTR2 agonist BIM-23023 and the selective D2R agonist BIM-53097 on human NET cell lines of heterogeneous origin. While having only minor effects on human pancreatic and bronchus carcinoid cells (BON1 and NCI-H727), BIM-23A758 induced significant antitumor effects in human midgut carcinoid cells (GOT1). These effects involved apoptosis induction as well as inhibition of mitogen-activated protein kinase and Akt signaling. Consistent with their antitumor response to BIM-23A758, GOT1 cells showed relatively high expression levels of SSTR2 and D2R mRNA. In particular, GOT1 cells highly express the short transcript variant of D2R. In contrast to BIM-23A758, the SSTR2/D2R chimeric compound BIM-23A760 as well as the individual SSTR2 and D2R agonistic compounds BIM-23023 and BIM-53097 induced no or only minor antitumor responses in the examined NET cell lines. Taken together, our findings suggest that the novel SSTR2/D2R chimeric compound BIM-23A758 might be a promising substance for the treatment of NETs highly expressing SSTR2 and D2R. In particular, a sufficient expression of the short transcript variant of DR2 might play a pivotal role for effective treatment. © 2013 S. Karger AG, Basel
- Subjects
SOMATOSTATIN receptors; DOPAMINE receptors; NEUROENDOCRINE tumors; CANCER cells; APOPTOSIS
- Publication
Neuroendocrinology, 2013, Vol 98, Issue 2, p128
- ISSN
0028-3835
- Publication type
Article
- DOI
10.1159/000353784