The cytotoxic effect of emetine and CGP-74514A studied with the hollow fiber model and ArrayScan assay in neuroendocrine tumors in vitro.

Abstract

Emetine and CGP-74514A have previously shown antitumor activity in neuroendocrine tumor cell lines. The aim of this study was to investigate the cytotoxic activity of the drugs in a three-dimensional model and to study if the mechanism of the cytotoxic activity was induction of apoptosis. An in vitro hollow fiber model was used to study the cytotoxic effect and a multiparametric high-content screening assay was used for measurement of apoptosis. The human pancreatic carcinoid cell line, BON-1 and the human typical and atypical bronchial carcinoid cell lines NCI-H727 and NCI-H720 were tested. Emetine and CGP-74514A showed higher antitumor activity on NCI-H720 compared to NCI-H727 and 3 day cultures were more sensitive than the 14 day cultures. A time- and dose-dependent activation of caspase-3 and increase in nuclear fragmentation and condensation were observed for the drugs in NCI-H727 and BON-1 using a multiparametric apoptosis assay. These results were confirmed with nuclear morphological examinations on microscopic slides. Emetine and CGP-74514A showed antitumor activity and induced caspase-3 activation with modest changes in nuclear morphology, indicating induction of apoptosis.

• Authors: Dhana E Larsson, Saadia B Hassan, Kjell Oberg, Dan Granberg
• Journal: Anti-cancer agents in medicinal chemistry (Anticancer Agents Med Chem) Vol. 12 Issue 7 Pg. 783-90 (Sep 2012) ISSN: 1875-5992 [Electronic] Netherlands
• PMID: 22263790 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• N(2)-(2-aminocyclohexyl)-N(6)-(3-chlorophenyl)-9-ethyl-9H-purine-2,6-diamine
• 2-Aminopurine
• Emetine

Topics

• 2-Aminopurine (analogs & derivatives, pharmacology)
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Drug Screening Assays, Antitumor (methods)
• Emetine (pharmacology)
• Humans
• Neuroendocrine Tumors (drug therapy, pathology)