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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
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
2012 (English)In: ANTI-CANCER AGENT ME, ISSN 1871-5206, Vol. 12, no 7, 783-790 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2012. Vol. 12, no 7, 783-790 p.
Keyword [en]
Apoptosis, Caspase-3, Hollow Fiber model, ArrayScan Assay, Emetine, CGP-74514A, Neuroendocrine tumor cell lines, BON-1, NCI-H727, NCI-H720, CDK inhibitor
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-187106ISI: 000310052900011OAI: oai:DiVA.org:uu-187106DiVA: diva2:573898
Available from: 2012-12-03 Created: 2012-12-03 Last updated: 2012-12-03Bibliographically approved

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Hassan, Saadia BashirÖberg, KjellGranberg, Dan

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