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Investigational New Drugs
Published in: Investigational New Drugs 4/2015

01-08-2015 | PRECLINICAL STUDIES

Three-dimensional and co-culture models for preclinical evaluation of metal-based anticancer drugs

Authors: Ekaterina Schreiber-Brynzak, Erik Klapproth, Christine Unger, Irene Lichtscheidl-Schultz, Simone Göschl, Sarah Schweighofer, Robert Trondl, Helmut Dolznig, Michael A. Jakupec, Bernhard K. Keppler

Published in: Investigational New Drugs | Issue 4/2015

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Summary

Background Hypoxic and necrotic regions that accrue within solid tumors in vivo are known to be associated with metastasis formation, radio- and chemotherapy resistance, and drug metabolism. Therefore, integration of these tumor characteristics into in vitro drug screening models is advantageous for any reliable investigation of the anticancer activity of novel drug candidates. In general, usage of cell culture models with in vivo like characteristics has become essential in preclinical drug studies and allows evaluation of complex problems such as tumor selectivity and anti-invasive properties of the drug candidates. Materials and Methods In this study, we investigated the anticancer activity of clinically approved, investigational and experimental drugs based on platinum (cisplatin, oxaliplatin and KP1537), gallium (KP46), ruthenium (KP1339) and lanthanum (KP772) in different cell culture models such as monolayers, multicellular spheroids, as well as invasion and metastasis models. Results Application of the Alamar Blue assay to multicellular spheroids and a spheroid-based invasion assay resulted in an altered rating of compounds with regard to their cytotoxicity and ability to inhibit invasion when compared with monolayer-based cytotoxicity and transwell assays. For example, the gallium-based drug candidate KP46 showed in spheroid cultures significantly enhanced properties to inhibit protrusion formation and fibroblast mediated invasiveness, and improved cancer cell selectivity. Conclusion Taken together, our results demonstrate the advantages of spheroid-based assays and underline the necessity of using different experimental models for reliable preclinical investigations assessing and better predicting the anticancer potential of new compounds.
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Metadata
Title
Three-dimensional and co-culture models for preclinical evaluation of metal-based anticancer drugs
Authors
Ekaterina Schreiber-Brynzak
Erik Klapproth
Christine Unger
Irene Lichtscheidl-Schultz
Simone Göschl
Sarah Schweighofer
Robert Trondl
Helmut Dolznig
Michael A. Jakupec
Bernhard K. Keppler
Publication date
01-08-2015
Publisher
Springer US
Published in
Investigational New Drugs / Issue 4/2015
Print ISSN: 0167-6997
Electronic ISSN: 1573-0646
DOI
https://doi.org/10.1007/s10637-015-0260-4

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