Drug toxicity assessment: cell proliferation versus cell death

Sazonova, Elena V.; Chesnokov, Mikhail S.; Zhivotovsky, Boris; Kopeina, Gelina S.

doi:10.1038/s41420-022-01207-x

Cited by 25 publications

(9 citation statements)

References 53 publications

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“…Therefore, MTT requires solubilization of insoluble formazan to determine its concentration by absorbance, whereas XTT does not require any solubilization. Therefore, the use of XTT is an excellent solution for the quantification of cells and their viability, as it greatly simplifies the procedure for measuring proliferation over MTT, reduces assay time, and increases the sensitivity of the assay [ 73 ]. In this study, the dose-dependent cell viabilities of human brain glioblastoma (U-118 MG) and human retinal pigment epithelium (ARPE-19) cell lines after administration of Ch/Q- and Ch/CA-Ag NPs were measured using XTT assay ( Figure 6 ).…”

Section: Resultsmentioning

confidence: 99%

Quercetin- and caffeic acid-functionalized chitosan-capped colloidal silver nanoparticles: one-pot synthesis, characterization, and anticancer and antibacterial activities

Kurt¹,

Olutaş²,

Avcıoğlu³

et al. 2023

Beilstein J. Nanotechnol.

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The presented study comprises the one-pot synthesis and the characterization of quercetin- and caffeic acid-functionalized chitosan-capped colloidal silver nanoparticles (Ch/Q- and Ch/CA-Ag NPs), and their antibacterial and anticancer activities. The formation of Ch/Q- and Ch/CA-Ag NPs has been confirmed by ultraviolet–visible (UV–vis) spectroscopy, Fourier-transform infrared (FTIR) spectroscopy, and transmission electron microscopy (TEM). The characteristic surface plasmon resonance (SPR) absorption band has been found at 417 and 424 nm for Ch/Q- and Ch/CA-Ag NPs, respectively. The formation of a chitosan shell comprising quercetin and caffeic acid, which surround the colloidal core Ag NPs, was confirmed by UV–vis, and FTIR analyses, and monitored by TEM microscopy. The size of nanoparticles has been determined as 11.2 and 10.3 nm for Ch/Q- and Ch/CA-Ag, respectively. The anticancer activity of Ch/Q- and Ch/CA-Ag NPs has been evaluated against U-118 MG (human glioblastoma) and ARPE-19 (human retinal pigment epithelium) cells. Both NPs showed anticancer activity, but Ch/Q-Ag NPs seemed to be more effective on cancer cell lines (U-118 MG) in comparison to healthy ones (ARPE-19). Furthermore, the antibacterial activity of Ch/Q- and Ch/CA-Ag NPs against Gram-negative (P. aeruginosa and E. coli) and Gram-positive (S. aureus and S. epidermidis) bacteria was determined, and dose-dependent antibacterial effects were found.

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Section: Resultsmentioning

confidence: 99%

Quercetin- and caffeic acid-functionalized chitosan-capped colloidal silver nanoparticles: one-pot synthesis, characterization, and anticancer and antibacterial activities

Kurt¹,

Olutaş²,

Avcıoğlu³

et al. 2023

Beilstein J. Nanotechnol.

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“…The Vero cell lines were used for research (African green monkey kidney epithelium) in vitro cytotoxicity by means of MTT test (Figure 9, 10) [26] . Results obtained demonstrate the weak toxicity of a hybrid 3 g , bearing chlorambucil (Figure 10).…”

Section: Resultsmentioning

confidence: 99%

“…The Vero cell lines were used for research (African green monkey kidney epithelium) in vitro cytotoxicity by means of MTT test (Figure 9, 10). [26] Results obtained demonstrate the weak toxicity of a hybrid 3 g, bearing chlorambucil (Figure 10). In the presence of hybrid 3 e containing salicylic acid and especially hybride 3 f bearing caffeic acid cell survival is decreased.…”

Section: Cytotoxicity Assaymentioning

confidence: 92%

Photocaging of Carboxylic Function Bearing Biomolecules by New Thiazole Derived Fluorophore

Gagarin,

Minin,

Shevyrin

et al. 2023

Chemistry A European J

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The design and synthesis of a new fluorophore containing an arylidene thiazole scaffold resulted in a compound with good photophysical characteristics. Furthermore, the thiazole C5‐methyl group was easily modified into specific functional groups (CH2Br and CH2OH) for the formation of a series of photocourier molecules containing model compounds (benzoic acids), as well as prodrugs, including salicylic acid, caffeic acid, and chlorambucil via a “benzyl” linker. Spectral characteristics (1Н, 13С NMR, and high‐resolution mass spectra) corresponded to the proposed structures. The photocourier molecules demonstrated absorption with high values of coefficient of molar extinction, exhibited contrasting green emission, and showed good dark stability. The mechanism of the photorelease was investigated through spectral analysis, HPLV‐HRMS, and supported by TD‐DFT calculations. The photoheterolysis and elimination of carboxylic acids were proved to occur in the excited state, yielding a carbocation as an intermediate moiety. The fluorophore structure provided stability to the carbocation through the delocalization of the positive charge via resonance structures. Viability assessment of Vero cells using the MTT‐test confirmed the weak cytotoxicity of prodrugs without irradiation and it increase upon UV‐light.

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“…Data obtained by different methods may have poor agreement 13,14 due to changes in cell metabolism 8 , adhesion, cell size and morphology 11 , or drug influence on substrate used for measurement. Optimization the consistency between NADH or ATP-based assays, measurements of cell area or LIVE/DEAD assays was addressed by numerous studies, providing either protocol optimizations, metric selection or method combination [15][16][17][18] . Advances in microscopy and image processing algorithms led to new high-content screening methods using fluorescence microscopy 19 , that also allow viable cells counting [20][21][22][23][24][25] .…”

Section: Introductionmentioning

confidence: 99%

Improving the power of drug toxicity measurements by quantitative nuclei imaging

Mikheeva,

Bogomolov,

Sementsov

et al. 2023

Preprint

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Imaging-based anticancer drug screens are becoming more prevalent due to development of automated fluorescent microscopes and imaging stations, as well as rapid advancements in imaging processing software. Automated cell imaging provides many benefits such as their ability to provide high-content data, modularity, dynamics recording and the fact that imaging is the most direct way to access cell viability and cell proliferation. However, currently most publicly available large-scale anticancer drugs screens, such as GDSC, CTRP and NCI-60, provide cell viability data measured by assays based on colorimetric or luminometric measurements of NADH or ATP levels. Although such datasets provide valuable data, it is unclear how well drug toxicity measurements can be integrated with imaging data. Here we explored the relations between drug toxicity data obtained by XTT assay, two quantitative nuclei imaging methods and trypan blue dye exclusion assay using a set of four cancer cell lines with different morphologies and 30 drugs with different mechanisms of action. We show that imaging-based approaches provide high accuracy and the differences between results obtained by different methods highly depend on drug mechanism of action. Selecting AUC metrics over IC50 or comparing data where significantly drugs reduced cell numbers noticeably improves consistency between methods. Using automated cell segmentation analysis and data-driven approach we show that XTT assay produces unreliable data for cell cycle and DNA repair inhibitors due induced cell size growth and increase in mitochondria activity. We also explored several benefits of image-based analysis such as ability to monitor cell number dynamics, dissect changes in mitochondria activity from cell proliferation, and ability to identify chromatin remodeling drugs. Finally, we will provide a web tool that allows comparing results obtained by different methods.

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Drug toxicity assessment: cell proliferation versus cell death

Cited by 25 publications

References 53 publications

Quercetin- and caffeic acid-functionalized chitosan-capped colloidal silver nanoparticles: one-pot synthesis, characterization, and anticancer and antibacterial activities

Quercetin- and caffeic acid-functionalized chitosan-capped colloidal silver nanoparticles: one-pot synthesis, characterization, and anticancer and antibacterial activities

Photocaging of Carboxylic Function Bearing Biomolecules by New Thiazole Derived Fluorophore

Improving the power of drug toxicity measurements by quantitative nuclei imaging

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