Publications Repository - Gdańsk University of Technology

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 densityrelated 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.

Authors

• dr Jan Lica,
• dr inż. Miłosz Wieczór link open in new tab ,
• dr Grzegorz Jan Grabe,
• Mateusz Heldt link open in new tab ,
• Marta Jancz link open in new tab ,
• Majus Misiak link open in new tab ,
• Dr inż. Katarzyna Gucwa,
• dr Wioletta Brankiewicz link open in new tab ,
• dr inż. Natalia Maciejewska link open in new tab ,
• dr inż. Anna Stupak link open in new tab ,
• prof. dr hab. inż. Maciej Bagiński link open in new tab ,
• Krzysztof Rolka,
• prof. dr hab. n. med. Andrzej Hellmann,
• prof. dr hab. inż. Andrzej Składanowski link open in new tab