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Evaluation of Impedance-Based Label-Free Technology as a Tool for Pharmacology and Toxicology Investigations

The use of label-free technologies based on electrical impedance is becoming more and more popular in drug discovery. Indeed, such a methodology allows the continuous monitoring of diverse cellular processes, including proliferation, migration, cytotoxicity and receptor-mediated signaling. The objec...

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Autores principales: Atienzar, Franck André, Gerets, Helga, Tilmant, Karen, Toussaint, Gaëlle, Dhalluin, Stéphane
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4263586/
https://www.ncbi.nlm.nih.gov/pubmed/25587404
http://dx.doi.org/10.3390/bios3010132
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author Atienzar, Franck André
Gerets, Helga
Tilmant, Karen
Toussaint, Gaëlle
Dhalluin, Stéphane
author_facet Atienzar, Franck André
Gerets, Helga
Tilmant, Karen
Toussaint, Gaëlle
Dhalluin, Stéphane
author_sort Atienzar, Franck André
collection PubMed
description The use of label-free technologies based on electrical impedance is becoming more and more popular in drug discovery. Indeed, such a methodology allows the continuous monitoring of diverse cellular processes, including proliferation, migration, cytotoxicity and receptor-mediated signaling. The objective of the present study was to further assess the usefulness of the real-time cell analyzer (RTCA) and, in particular, the xCELLigence platform, in the context of early drug development for pharmacology and toxicology investigations. In the present manuscript, four cellular models were exposed to 50 compounds to compare the cell index generated by RTCA and cell viability measured with a traditional viability assay. The data revealed an acceptable correlation (ca. 80%) for both cell lines (i.e., HepG2 and HepaRG), but a lack of correlation (ca. 55%) for the primary human and rat hepatocytes. In addition, specific RTCA profiles (signatures) were generated when HepG2 and HepaRG cells were exposed to calcium modulators, antimitotics, DNA damaging and nuclear receptor agents, with a percentage of prediction close to 80% for both cellular models. In a subsequent experiment, HepG2 cells were exposed to 81 proprietary UCB compounds known to be genotoxic or not. Based on the DNA damaging signatures, the RTCA technology allowed the detection of ca. 50% of the genotoxic compounds (n = 29) and nearly 100% of the non-genotoxic compounds (n = 52). Overall, despite some limitations, the xCELLigence platform is a powerful and reliable tool that can be used in drug discovery for toxicity and pharmacology studies.
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spelling pubmed-42635862015-01-13 Evaluation of Impedance-Based Label-Free Technology as a Tool for Pharmacology and Toxicology Investigations Atienzar, Franck André Gerets, Helga Tilmant, Karen Toussaint, Gaëlle Dhalluin, Stéphane Biosensors (Basel) Article The use of label-free technologies based on electrical impedance is becoming more and more popular in drug discovery. Indeed, such a methodology allows the continuous monitoring of diverse cellular processes, including proliferation, migration, cytotoxicity and receptor-mediated signaling. The objective of the present study was to further assess the usefulness of the real-time cell analyzer (RTCA) and, in particular, the xCELLigence platform, in the context of early drug development for pharmacology and toxicology investigations. In the present manuscript, four cellular models were exposed to 50 compounds to compare the cell index generated by RTCA and cell viability measured with a traditional viability assay. The data revealed an acceptable correlation (ca. 80%) for both cell lines (i.e., HepG2 and HepaRG), but a lack of correlation (ca. 55%) for the primary human and rat hepatocytes. In addition, specific RTCA profiles (signatures) were generated when HepG2 and HepaRG cells were exposed to calcium modulators, antimitotics, DNA damaging and nuclear receptor agents, with a percentage of prediction close to 80% for both cellular models. In a subsequent experiment, HepG2 cells were exposed to 81 proprietary UCB compounds known to be genotoxic or not. Based on the DNA damaging signatures, the RTCA technology allowed the detection of ca. 50% of the genotoxic compounds (n = 29) and nearly 100% of the non-genotoxic compounds (n = 52). Overall, despite some limitations, the xCELLigence platform is a powerful and reliable tool that can be used in drug discovery for toxicity and pharmacology studies. MDPI 2013-03-15 /pmc/articles/PMC4263586/ /pubmed/25587404 http://dx.doi.org/10.3390/bios3010132 Text en © 2013 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Atienzar, Franck André
Gerets, Helga
Tilmant, Karen
Toussaint, Gaëlle
Dhalluin, Stéphane
Evaluation of Impedance-Based Label-Free Technology as a Tool for Pharmacology and Toxicology Investigations
title Evaluation of Impedance-Based Label-Free Technology as a Tool for Pharmacology and Toxicology Investigations
title_full Evaluation of Impedance-Based Label-Free Technology as a Tool for Pharmacology and Toxicology Investigations
title_fullStr Evaluation of Impedance-Based Label-Free Technology as a Tool for Pharmacology and Toxicology Investigations
title_full_unstemmed Evaluation of Impedance-Based Label-Free Technology as a Tool for Pharmacology and Toxicology Investigations
title_short Evaluation of Impedance-Based Label-Free Technology as a Tool for Pharmacology and Toxicology Investigations
title_sort evaluation of impedance-based label-free technology as a tool for pharmacology and toxicology investigations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4263586/
https://www.ncbi.nlm.nih.gov/pubmed/25587404
http://dx.doi.org/10.3390/bios3010132
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