Title:The Cytotoxic Effect of Emetine and CGP-74514A Studied with the Hollow Fiber Model and ArrayScan Assay in Neuroendocrine Tumors In Vitro
Volume: 12
Issue: 7
Author(s): Dhana E. Larsson, Saadia B. Hassan, Kjell Oberg and Dan Granberg
Affiliation:
Keywords:
Apoptosis, Caspase-3, Hollow Fiber model, ArrayScan Assay, Emetine, CGP-74514A, Neuroendocrine tumor cell lines, BON-1,
NCI-H727, NCI-H720, CDK inhibitor.
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.
