Journal
ANALYST
Volume 140, Issue 10, Pages 3623-3629Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c5an00097a
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Funding
- EU FP7 project EXCELL [NMP4-SL-2008-214706]
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We investigated the combined effect of the initial cell density (12 500, 35 000, 75 000, and 100 000 cells cm(-2)) and concentration of the anti-cancer drug doxorubicin on HeLa cells by performing time-dependent cytotoxicity assays using real-time electrochemical impedance spectroscopy. A correlation between the rate of cell death and the initial cell seeding density was found at 2.5 mu M doxorubicin concentration, whereas this was not observed at 5 or 100 mu M. By sensing the changes in the cell-substrate interaction using impedance spectroscopy under static conditions, the onset of cytotoxicity was observed 5 h earlier than when using a standard colorimetric end-point assay (MTS) which measures changes in the mitochondrial metabolism. Furthermore, with the MTS assay no cytotoxicity was observed after 15 h of incubation with 2.5 mu M doxorubicin, whereas the impedance showed at this time point cell viability that was below 25%. These results indicate that impedance detection reveals cytotoxic events undetectable when using the MTS assay, highlighting the importance of combining impedance detection with traditional drug toxicity assays towards a more in depth understanding of the effect of anti-cancer drugs on in vitro assays. Moreover, the detection of doxorubicin induced toxicity determined with impedance under static conditions proved to be 6 times faster than in perfusion culture.
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