Effective Drug Concentration and Selectivity Depends on Fraction of Primitive Cells
| Autor: | Krzysztof Rolka, Mateusz Heldt, Marta Jancz, Andrzej Hellmann, Miłosz Wieczór, Andrzej Skladanowski, Jan Lica, Katarzyna Gucwa, Anna Stupak, Majus Misiak, Wioletta Brankiewicz, Natalia Maciejewska, Maciej Baginski, Grzegorz J Grabe |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Drug
primitive cancer cellular stages selectivity index QH301-705.5 media_common.quotation_subject Cell Primitive cell Antineoplastic Agents Cell Count C-123 Catalysis Article Flow cytometry effective drug concentration Inorganic Chemistry Inhibitory Concentration 50 cell culture density-dependent cytological stage profile Cancer stem cell Cell Line Tumor medicine Idarubicin Humans Physical and Theoretical Chemistry Biology (General) Molecular Biology drug screening platform QD1-999 Spectroscopy media_common Neoplasm Staging medicine.diagnostic_test Chemistry Bortezomib Organic Chemistry General Medicine primitive acute myeloid leukemia cellular stages Computer Science Applications medicine.anatomical_structure Cell Transformation Neoplastic Drug development Biophysics Reactive Oxygen Species medicine.drug |
| Zdroj: | International Journal of Molecular Sciences, Vol 22, Iss 4931, p 4931 (2021) International Journal of Molecular Sciences Volume 22 Issue 9 |
| ISSN: | 1661-6596 1422-0067 |
| Popis: | Poor efficiency of chemotherapeutics in the eradication of Cancer Stem Cells (CSCs) has been driving the search for more active and specific compounds. In this work, we show how cell density-dependent stage culture profiles can be used in drug development workflows to achieve more robust drug activity (IC50 and EC50) results. Using flow cytometry and light microscopy, we characterized the cytological stage profiles of the HL-60-, A-549-, and HEK-293-derived sublines with a focus on their primitive cell content. We then used a range of cytotoxic substances—C-123, bortezomib, idarubicin, C-1305, doxorubicin, DMSO, and ethanol—to highlight typical density-related issues accompanying drug activity determination. We also showed that drug EC50 and selectivity indices normalized to primitive cell content are more accurate activity measurements. We tested our approach by calculating the corrected selectivity index of a novel chemotherapeutic candidate, C-123. Overall, our study highlights the usefulness of accounting for primitive cell fractions in the assessment of drug efficiency. |
| Databáze: | OpenAIRE |
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