Effective Drug Concentration and Selectivity Depends on Fraction of Primitive Cells - Publikacja - MOST Wiedzy

Twoje konto

zaloguj

Wyszukiwarka

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.

Cytowania

  • 3 2

    CrossRef

  • 0

    Web of Science

  • 3 3

    Scopus

Autorzy (14)

Cytuj jako

Pełna treść

pobierz publikację
pobrano 70 razy
Wersja publikacji
Accepted albo Published Version
Licencja
Creative Commons: CC-BY otwiera się w nowej karcie

Słowa kluczowe

Informacje szczegółowe

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 164 razy

Publikacje, które mogą cię zainteresować

Cell Density-Dependent Cytological Stage Profile and Its Application for a Screen of Cytostatic Agents Active Toward Leukemic Stem Cells

2018

Enhanced Activity of P4503A4 and UGT1A10 Induced by Acridinone Derivatives C-1305 and C-1311 in MCF-7 and HCT116 Cancer Cells: Consequences for the Drugs’ Cytotoxicity, Metabolism and Cellular Response

2020

Metabolism of antitumour agent 1-nitroacridine derivative, C-1748 in pancreatic cancer cell lines

2015

Metabolic transformation of antitumor acridinone C-1305 but not C-1311 via selective cellular expression of UGT1A10 increases cytotoxic response: implications for clinical use.

  • M. Pawłowska,
  • R. Chu,
  • B. Fedejko-Kap
  • + 4 autorów
2013
Meta Tagi