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

Larsson DE,Hassan SB,Oberg K,Granberg D

doi

10.2174/187152012802650147

subject

Has Abstract

pub_date

2012-09-01 00:00:00

pages

783-90

issue

7

eissn

1871-5206

issn

1875-5992

pii

ACAMC-EPUB-20120119-003

journal_volume

12

pub_type

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