Details

Autor(en) / Beteiligte

• Lica, Jan Jakub
• Wieczór, Miłosz
• Grabe, Grzegorz Jan
• Heldt, Mateusz
• Jancz, Marta
• Misiak, Majus
• Gucwa, Katarzyna
• Brankiewicz, Wioletta
• Maciejewska, Natalia
• Stupak, Anna
• Bagiński, Maciej
• Rolka, Krzysztof
• Hellmann, Andrzej
• Składanowski, Andrzej

Titel

Effective Drug Concentration and Selectivity Depends on Fraction of Primitive Cells

Ist Teil von

• International journal of molecular sciences, 2021-05, Vol.22 (9), p.4931

Ort / Verlag

Basel: MDPI AG

Erscheinungsjahr

2021

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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.