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A new approach for the assessment of the toxicity of polyphenol-rich compounds with the use of high content screening analysis

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dc.contributor.author Boncler, Magdalena
dc.contributor.author Golanski, Jacek
dc.contributor.author Lukasiak, Magdalena
dc.contributor.author Redzynia, Malgorzata
dc.contributor.author Dastych, Jaroslaw
dc.contributor.author Watala, Cezary
dc.date.accessioned 2017-06-05T09:24:04Z
dc.date.available 2017-06-05T09:24:04Z
dc.date.issued 2017
dc.identifier.uri http://hdl.handle.net/11652/1482
dc.description Proteon Pharmaceuticals and one of the co-authors (Magdalena Lukasiak) were responsible mainly for cell culture and for performing of HCS analysis. Raw data gathered by Proteon Pharmaceuticals were further analyzed by co-workers of the Medical University of Lodz). en_EN
dc.description.abstract The toxicity of in vitro tested compounds is usually evaluated based on EC50 values calculated from dose-response curves. However, there is a large group of compounds for which a standard four-parametric sigmoid curve fitting may be inappropriate for estimating EC50. In the present study, 22 polyphenol-rich compounds were prioritized from the least to the most toxic based on the total area under and over the dose-response curves (AUOC) in relation to baselines. The studied compounds were ranked across three key cell indicators (mitochondrial membrane potential, cell membrane integrity and nuclear size) in a panel of five cell lines (HepG2, Caco-2, A549, HMEC-1, and 3T3), using a high-content screening (HCS) assay. Regarding AUOC score values, naringin (negative control) was the least toxic phenolic compound. Aronox, spent hop extract and kale leaf extract had very low cytotoxicity with regard to mitochondrial membrane potential and cell membrane integrity, as well as nuclear morphology (nuclear area). Kaempferol (positive control) exerted strong cytotoxic effects on the mitochondrial and nuclear compartments. Extracts from buckthorn bark, walnut husk and hollyhock flower were highly cytotoxic with regard to the mitochondrion and cell membrane, but not the nucleus. We propose an alternative algorithm for the screening of a large number of agents and for identifying those with adverse cellular effects at an early stage of drug discovery, using high content screening analysis. This approach should be recommended for series of compounds producing a non-sigmoidal cell response, and for agents with unknown toxicity or mechanisms of action. en_EN
dc.description.sponsorship info:eu-repo/grantAgreement/[European Regional Development Fund Innovative Economy Operational Programme]/UDA-POIG.01.03.01-10-129/08-00/[Production of polyphenol extracts of plant origin with antiplatelet and cardioprotective properties – FLAWOPIRYNA] en_EN
dc.description.sponsorship Proteon Pharmaceuticals
dc.format.mimetype application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
dc.language.iso en
dc.rights Creative Commons Attribution 4.0 International
dc.rights.uri info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/licenses/by/4.0
dc.subject cytotoxicity en_EN
dc.subject high content analysis en_EN
dc.subject plant compounds en_EN
dc.subject human cancer cells en_EN
dc.subject human endothelial cells en_EN
dc.title A new approach for the assessment of the toxicity of polyphenol-rich compounds with the use of high content screening analysis en_EN
dc.title.alternative A new approach to the study of toxicity of polyphenol-rich compounds en_EN
dc.type Dataset en_EN
dc.contributor.institution Medical University of Lodz, Department of Haemostasis and Haemostatic Disorders en_EN
dc.contributor.institution Proteon Pharmaceuticals SA en_EN
dc.contributor.institution Lodz University of Technology, Faculty of Biotechnology and Food Sciences, Institute of Technical Biochemistry en_EN
dc.contributor.institution Polish Academy of Sciences, Institute of Medical Biology, Laboratory of Cellular Immunology en_EN

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