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

2021 ◽  
Vol 12 ◽  
Author(s):  
D.A. Skvortsov ◽  
M.A. Kalinina ◽  
I.V. Zhirkina ◽  
L.A. Vasilyeva ◽  
Y.A. Ivanenkov ◽  
...  
Keyword(s):  
Cancer Cells ◽  
High Throughput ◽  
High Throughput Screening ◽  
Fluorescent Proteins ◽  
Carcinoma Cells ◽  
Anticancer Compounds ◽  
Fluorescent Cell ◽  
Lung Carcinoma Cells ◽  
Cancerous Cells ◽  
Independent Assay

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.

scholarly journals Fer and FerT Govern Mitochondrial Susceptibility to Metformin and Hypoxic Stress in Colon and Lung Carcinoma Cells

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 97
Author(s):  
Odeya Marciano ◽  
Linoy Mehazri ◽  
Sally Shpungin ◽  
Alexander Varvak ◽  
Eldad Zacksenhaus ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Aerobic Glycolysis ◽  
Metastatic Cancer ◽  
Carcinoma Cells ◽  
Metabolic Adaptation ◽  
Hypoxic Stress ◽  
Lung Carcinoma Cells ◽  
Metabolic Role ◽  
Highly Sensitive ◽  
Anticancer Treatment

Aerobic glycolysis is an important metabolic adaptation of cancer cells. However, there is growing evidence that reprogrammed mitochondria also play an important metabolic role in metastatic dissemination. Two constituents of the reprogrammed mitochondria of cancer cells are the intracellular tyrosine kinase Fer and its cancer- and sperm-specific variant, FerT. Here, we show that Fer and FerT control mitochondrial susceptibility to therapeutic and hypoxic stress in metastatic colon (SW620) and non-small cell lung cancer (NSCLC-H1299) cells. Fer- and FerT-deficient SW620 and H1299 cells (SW∆Fer/FerT and H∆Fer/FerT cells, respectively) become highly sensitive to metformin treatment and to hypoxia under glucose-restrictive conditions. Metformin impaired mitochondrial functioning that was accompanied by ATP deficiency and robust death in SW∆Fer/FerT and H∆Fer/FerT cells compared to the parental SW620 and H1299 cells. Notably, selective knockout of the fer gene without affecting FerT expression reduced sensitivity to metformin and hypoxia seen in SW∆Fer/FerT cells. Thus, Fer and FerT modulate the mitochondrial susceptibility of metastatic cancer cells to hypoxia and metformin. Targeting Fer/FerT may therefore provide a novel anticancer treatment by efficient, selective, and more versatile disruption of mitochondrial function in malignant cells.

scholarly journals Sensitive ADAR editing reporter in cancer cells enables high-throughput screening of small molecule libraries

2018 ◽  
Vol 47 (4) ◽  
pp. e22-e22 ◽  
Author(s):  
Kajsa Fritzell ◽  
Li-Di Xu ◽  
Magdalena Otrocka ◽  
Claes Andréasson ◽  
Marie Öhman
Keyword(s):  
Cancer Cells ◽  
Small Molecule ◽  
High Throughput ◽  
High Throughput Screening ◽  
Small Molecule Libraries ◽  
Adar Editing

High throughput screening to identify new compounds with proapoptotic activity in resistant lung cancer cells

2015 ◽  
Vol 32 (3) ◽  
pp. 324
Author(s):  
P. Gilson ◽  
L. Vanwonterghem ◽  
F. Mahuteau ◽  
S. Piguel ◽  
J.L. Coll ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
High Throughput ◽  
High Throughput Screening ◽  
Lung Cancer Cells ◽  
New Compounds

scholarly journals Phytochemicals potently inhibit migration of metastatic breast cancer cells

2015 ◽  
Vol 7 (7) ◽  
pp. 792-800 ◽  
Author(s):  
Stephanie Lemmo Ham ◽  
Samila Nasrollahi ◽  
Kush N. Shah ◽  
Andrew Soltisz ◽  
Sailaja Paruchuri ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Cells ◽  
High Throughput ◽  
High Throughput Screening ◽  
Breast Cancer Cells ◽  
Metastatic Breast ◽  
Natural Compounds ◽  
Screening Technology

A high throughput screening technology enables identifying natural compounds, phytochemicals, that potently inhibit migration of metastatic breast cancer cells.

scholarly journals Sorting out antibiotics' mechanisms of action: a double fluorescent protein reporter for high throughput screening of ribosome and DNA biosynthesis inhibitors

2016 ◽  
pp. AAC.02117-16 ◽  
Author(s):  
Ilya A. Osterman ◽  
Ekaterina S. Komarova ◽  
Dmitry I. Shiryaev ◽  
Ilya A. Korniltsev ◽  
Irina M. Khven ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Protein Gene ◽  
Fluorescent Protein ◽  
Fluorescent Proteins ◽  
Cost Effective ◽  
High Signal ◽  
Red Fluorescent Protein ◽  
Reporter System ◽  
Ribosome Stalling

In order to accelerate drug discovery, a simple, reliable and cost-effective system for high-throughput identification of a potential antibiotic mechanism of action is required. To facilitate such screening of new antibiotics, we created a double reporter system for not only antimicrobial activity detection, but also for simultaneous sorting of potential antimicrobials into those that cause ribosome stalling, and others that induce SOS response due to DNA damage. In this reporter system the red fluorescent protein generfpwas placed under the control of the SOS-induciblesulApromoter. The far-red fluorescent protein genekatushka2Swas inserted downstream the tryptophan attenuator where two tryptophan codons were replaced by alanine codons, with simultaneous replacement of the complementary part of the attenuator, to preserve the ability to form secondary structures that influence transcription termination. This genetically modified attenuator makes possible Katushka2S expression only upon exposure to any ribosome stalling compounds. The application of red and far-red fluorescent proteins provides a high signal-to-background ratio without any need in enzymatic substrates for detection of the reporter activity. This reporter was shown to be efficient in high-throughput screening of both synthetic and natural chemicals.

scholarly journals High-throughput Screening for Identification of Inhibitors of EpCAM-Dependent Growth of Hepatocellular Carcinoma Cells

2013 ◽  
Vol 82 (2) ◽  
pp. 131-139 ◽  
Author(s):  
Curtis J. Henrich ◽  
Anuradha Budhu ◽  
Zhipeng Yu ◽  
Jason R. Evans ◽  
Ekaterina I. Goncharova ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
High Throughput ◽  
High Throughput Screening ◽  
Carcinoma Cells ◽  
Hepatocellular Carcinoma Cells ◽  
Dependent Growth
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