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The cytotoxic effect of emetine and CGP-74514A studied with the Hollow Fiber Model and ArrayScan Assay in neuroendocrine tumors In Vitro.
MedLine Citation:
PMID:  22263790     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Emetine and CGP-74514A has 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
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-19
Journal Detail:
Title:  Anti-cancer agents in medicinal chemistry     Volume:  -     ISSN:  1875-5992     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101265649     Medline TA:  Anticancer Agents Med Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Medical Sciences, Section of Endocrine Oncology, University Hospital, S-751 85 Uppsala, Sweden. dhana.larsson@medsci.uu.se.
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