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

Uproszczony widok
dc.contributor.authorBoncler, Magdalena
dc.contributor.authorGolanski, Jacek
dc.contributor.authorLukasiak, Magdalena
dc.contributor.authorRedzynia, Malgorzata
dc.contributor.authorDastych, Jaroslaw
dc.contributor.authorWatala, Cezary
dc.contributor.authorAffiliationMedical University of Lodz. Department of Haemostasis and Haemostatic Disorders.en_EN
dc.contributor.authorAffiliationProteon Pharmaceuticals SAen_EN
dc.contributor.authorAffiliationLodz University of Technology. Faculty of Biotechnology and Food Sciences. Institute of Technical Biochemistry.en_EN
dc.contributor.authorAffiliationPolish Academy of Sciences. Institute of Medical Biology. Laboratory of Cellular Immunology.en_EN
dc.date.accessioned2017-09-11T07:15:28Z
dc.date.available2017-09-11T07:15:28Z
dc.date.issued2017
dc.descriptionRaw data gathered by Proteon Pharmaceuticals were further analyzed by co-workers of the Medical University of Lodz.en_EN
dc.descriptionProteon 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.abstractThe 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.sponsorshipProteon Pharmaceuticals
dc.description.sponsorshipinfo: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.format.mimetypeapplication/pdf
dc.identifier.citationhttps://doi.org/10.1371/journal.pone.0180022
dc.identifier.citationPLoS One. 2017 Jun 29;12(6):e0180022
dc.identifier.urihttp://hdl.handle.net/11652/1482
dc.identifier.urihttp://hdl.handle.net/11652/1722
dc.language.isoen
dc.relation.ispartofPLoS One
dc.rightsCreative Commons Attribution 4.0 International
dc.rights.uriinfo:eu-repo/semantics/openAccess
dc.rights.urihttp://creativecommons.org/licenses/by/4.0
dc.subjectcytotoxicityen_EN
dc.subjecthigh content analysisen_EN
dc.subjectplant compoundsen_EN
dc.subjecthuman cancer cellsen_EN
dc.subjecthuman endothelial cellsen_EN
dc.titleA new approach for the assessment of the toxicity of polyphenol-rich compounds with the use of high content screening analysisen_EN
dc.title.alternativeA new approach to the study of toxicity of polyphenol-rich compoundsen_EN
dc.typeArticleen_EN
dc.typeArtykułpl_PL

Pliki

Oryginalne pliki
Teraz wyświetlane 1 - 1 z 1
Brak miniatury
Nazwa:
Approach_assessment_toxicity_polyphenol_rich_compounds_Boncler_2017.pdf
Rozmiar:
3.72 MB
Format:
Adobe Portable Document Format
Opis:
Pobierz

Kolekcje

Inne (WBiNoŻ)