The Cytotoxic Effect of Emetine and CGP-74514A Studied with the Hollow Fiber Model and ArrayScan Assay in Neuroendocrine Tumors In Vitro
2012 (English)In: ANTI-CANCER AGENT ME, ISSN 1871-5206, Vol. 12, no 7, 783-790 p.Article in journal (Refereed) Published
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.
Apoptosis, Caspase-3, Hollow Fiber model, ArrayScan Assay, Emetine, CGP-74514A, Neuroendocrine tumor cell lines, BON-1, NCI-H727, NCI-H720, CDK inhibitor
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-187106ISI: 000310052900011OAI: oai:DiVA.org:uu-187106DiVA: diva2:573898