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Effective Drug Concentration and Selectivity Depends on Fraction of Primitive Cells

Abstrakt

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.

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Kategoria:
Publikacja w czasopiśmie
Typ:
artykuły w czasopismach
Opublikowano w:
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES nr 22,
ISSN: 1661-6596
Język:
angielski
Rok wydania:
2021
Opis bibliograficzny:
Lica J., Wieczór M., Grabe G. J., Heldt M., Jancz M., Misiak M., Gucwa K., Brankiewicz W., Maciejewska N., Stupak A., Bagiński M., Rolka K., Hellmann A., Składanowski A.: Effective Drug Concentration and Selectivity Depends on Fraction of Primitive Cells// INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES -Vol. 22,iss. 9 (2021), s.4931-
DOI:
Cyfrowy identyfikator dokumentu elektronicznego (otwiera się w nowej karcie) 10.3390/ijms22094931
Źródła finansowania:
  • Department of Molecular Biochemistry, Faculty of Chemistry, University of Gdansk, fund number: 531-T060-D737-21
Weryfikacja:
Politechnika Gdańska

wyświetlono 168 razy

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