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Frontiers in Pharmacology, volume 12

From Toxicity to Selectivity: Coculture of the Fluorescent Tumor and Non-Tumor Lung Cells and High-Throughput Screening of Anticancer Compounds

Skvortsov D A 1, 2
Kalinina M A 3
Zhirkina I V 1
Vasilyeva L A 1
Ivanenkov Y A 1, 4
Sergiev P V 1, 3
Dontsova O. A. 1, 3, 5
Publication typeJournal Article
Publication date2021-10-11
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor5.6
ISSN16639812
Pharmacology
Pharmacology (medical)
Abstract

For the search of anticancer compounds in modern large chemical libraries, new approaches are of great importance. Cocultivation of the cells of tumor and non-tumor etiology may reveal specific action of chemicals on cancer cells and also take into account some effects of the tumor cell’s microenvironment. The fluorescent cell cocultivation test (FCCT) has been developed for screening of substances that are selectively cytotoxic on cancerous cells. It is based on the mixed culture of lung carcinoma cells A549’_EGFP and noncancerous fibroblasts of lung VA13_Kat, expressing different fluorescent proteins. Analysis of the cells was performed with the high-resolution scanner to increase the detection rate. The combination of cocultivation of cells with scanning of fluorescence reduces the experimental protocol to three steps: cells seeding, addition of the substance, and signal detection. The FCCT analysis does not disturb the cells and is compatible with other cell-targeted assays. The suggested method has been adapted for a high-throughput format and applied for screening of 2,491 compounds. Three compounds were revealed to be reproducibly selective in the FCCT although they were invisible in cytotoxicity tests in individual lines. Six structurally diverse indole, coumarin, sulfonylthiazol, and rifampicin derivatives were found and confirmed with an independent assay (MTT) to be selectively cytotoxic to cancer cells in the studied model.

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Skvortsov D. A. et al. From Toxicity to Selectivity: Coculture of the Fluorescent Tumor and Non-Tumor Lung Cells and High-Throughput Screening of Anticancer Compounds // Frontiers in Pharmacology. 2021. Vol. 12.
GOST all authors (up to 50) Copy
Skvortsov D. A., Kalinina M. A., Zhirkina I. V., Vasilyeva L. A., Ivanenkov Y. A., Sergiev P. V., Dontsova O. A. From Toxicity to Selectivity: Coculture of the Fluorescent Tumor and Non-Tumor Lung Cells and High-Throughput Screening of Anticancer Compounds // Frontiers in Pharmacology. 2021. Vol. 12.
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RIS Copy
TY - JOUR
DO - 10.3389/fphar.2021.713103
UR - https://doi.org/10.3389%2Ffphar.2021.713103
TI - From Toxicity to Selectivity: Coculture of the Fluorescent Tumor and Non-Tumor Lung Cells and High-Throughput Screening of Anticancer Compounds
T2 - Frontiers in Pharmacology
AU - Skvortsov, D A
AU - Kalinina, M A
AU - Zhirkina, I V
AU - Vasilyeva, L A
AU - Ivanenkov, Y A
AU - Sergiev, P V
AU - Dontsova, O. A.
PY - 2021
DA - 2021/10/11 00:00:00
PB - Frontiers Media S.A.
VL - 12
PMID - 34707495
SN - 1663-9812
ER -
BibTex
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BibTex Copy
@article{2021_Skvortsov,
author = {D A Skvortsov and M A Kalinina and I V Zhirkina and L A Vasilyeva and Y A Ivanenkov and P V Sergiev and O. A. Dontsova},
title = {From Toxicity to Selectivity: Coculture of the Fluorescent Tumor and Non-Tumor Lung Cells and High-Throughput Screening of Anticancer Compounds},
journal = {Frontiers in Pharmacology},
year = {2021},
volume = {12},
publisher = {Frontiers Media S.A.},
month = {oct},
url = {https://doi.org/10.3389%2Ffphar.2021.713103},
doi = {10.3389/fphar.2021.713103}
}
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