title: 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.affiliation: Department of Medical Sciences, Section of Endocrine Oncology, University Hospital, S-751 85 Uppsala, Sweden. dhana.larsson@medsci.uu.se
authors.forename: Dhana E
authors.initials: DE
authors.lastname: Larsson
authors.forename: Saadia B
authors.initials: SB
authors.lastname: Hassan
authors.forename: Kjell
authors.initials: K
authors.lastname: Oberg
authors.forename: Dan
authors.initials: D
authors.lastname: Granberg
mesh_terms: D015075:2-Aminopurine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D004640:Emetine / Q000494:pharmacology*; D006801:Humans; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; C469937:N(2)-(2-aminocyclohexyl)-N(6)-(3-chlorophenyl)-9-ethyl-9H-purine-2,6-diamine; D015075:2-Aminopurine; D004640:Emetine