Anti-Cancer Agents in Medicinal Chemistry

(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Michelle Prudhomme  
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex
France

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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

Author(s): Dhana E. Larsson, Saadia B. Hassan, Kjell Oberg, Dan Granberg.

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.

Keywords: Apoptosis, Caspase-3, Hollow Fiber model, ArrayScan Assay, Emetine, CGP-74514A, Neuroendocrine tumor cell lines, BON-1, NCI-H727, NCI-H720, CDK inhibitor.

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Article Details

VOLUME: 12
ISSUE: 7
Year: 2012
Page: [783 - 790]
Pages: 8
DOI: 10.2174/187152012802650147
Price: $58