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Int. J. Mol. Sci. 2015, 16(11), 27044-27057; doi:10.3390/ijms161126014

Online Measurement of Real-Time Cytotoxic Responses Induced by Multi-Component Matrices, such as Natural Products, through Electric Cell-Substrate Impedance Sensing (ECIS)

1
Discipline of Pharmaceutical Biology, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, 00014 Helsinki, Finland
2
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY 10461, USA
3
Laboratory of Organic Chemistry and Chemical Biology, Department of Chemistry, University of Turku, 20014 Turku, Finland
*
Author to whom correspondence should be addressed.
Academic Editor: Maurizio Battino
Received: 15 October 2015 / Revised: 2 November 2015 / Accepted: 4 November 2015 / Published: 12 November 2015
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
View Full-Text   |   Download PDF [1023 KB, uploaded 12 November 2015]   |  

Abstract

Natural products are complex matrices of compounds that are prone to interfere with the label-dependent methods that are typically used for cytotoxicity screenings. Here, we developed a label-free Electric Cell-substrate Impedance Sensing (ECIS)-based cytotoxicity assay that can be applied in the assessment of the cytotoxicity of natural extracts. The conditions to measure the impedance using ECIS were first optimized in mice immortalized hypothalamic neurons GT1-7 cells. The performance of four natural extracts when tested using three conventional cytotoxicity assays in GT1-7 cells, was studied. Betula pendula (silver birch tree) was found to interfere with all of the cytotoxicity assays in which labels were applied. The silver birch extract was also proven to be cytotoxic and, thus, served as a proof-of-concept for the use of ECIS. The extract was fractionated and the ECIS method permitted the distinction of specific kinetic patterns of cytotoxicity on the fractions as well as the extract’s pure constituents. This study offers evidence that ECIS is an excellent tool for real-time monitoring of the cytotoxicity of complex extracts that are difficult to work with using conventional (label-based) assays. Altogether, it offers a very suitable cytotoxicity-screening assay making the work with natural products less challenging within the drug discovery workflow. View Full-Text
Keywords: ECIS; cytotoxicity; impedance; label-free; natural extracts; screening ECIS; cytotoxicity; impedance; label-free; natural extracts; screening
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Fallarero, A.; Batista-González, A.E.; Hiltunen, A.K.; Liimatainen, J.; Karonen, M.; Vuorela, P.M. Online Measurement of Real-Time Cytotoxic Responses Induced by Multi-Component Matrices, such as Natural Products, through Electric Cell-Substrate Impedance Sensing (ECIS). Int. J. Mol. Sci. 2015, 16, 27044-27057.

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