Comparative endothelial profiling of doxorubicin and daunorubicin in cultured endothelial cells
PBN-AR
Instytucja
Instytut Fizyki Jądrowej im. Henryka Niewodniczańskiego Polskiej Akademii Nauk
Informacje podstawowe
Główny język publikacji
en
Czasopismo
TOXICOLOGY IN VITRO
ISSN
0887-2333
EISSN
Wydawca
DOI
URL
Rok publikacji
2015
Numer zeszytu
3
Strony od-do
512-521
Numer tomu
29
Identyfikator DOI
Liczba arkuszy
Autorzy
(liczba autorów: 10)
Pozostali autorzy
+ 8
Autorzy przekładu
(liczba autorów przekładu: 0)
Słowa kluczowe
en
Doxorubicin
Daunorubicin
Cytotoxicity
Endothelium
High-content screening
Streszczenia
Język
en
Treść
Although anthracycline antibiotics have been successfully used for nearly half a century in the treatment of various malignancies, their use is limited by their cardiac and vascular toxicities, and the mechanisms of these toxicities are still not entirely clear. Herein, we comprehensively characterized cytotoxic effects of two structurally related anthracyclines, doxorubicin and daunorubicin. In nanomolar concentrations, both drugs induced DNA damage and increased nuclear area that were associated with their accumulation in the nucleus (doxorubicin ⩾50 nM and daunorubicin ⩾25 nM) as evidence by Raman microspectroscopy at 3820–4245 cm−1. At low micromolar concentrations, doxorubicin (⩾5 μM) and daunorubicin (⩾1 μM) increased the generation of reactive oxygen species, decreased intracellular reduced glutathione, induced an alteration in endothelial elasticity and caused a reorganization of the F-actin cytoskeleton. In isolated mouse aortic rings, doxorubicin (⩾50 μM) was less potent than daunorubicin (⩾5 μM) in impairing the endothelium-dependent response. In summary, using a comprehensive endothelial profiling approach, we demonstrated clear-cut differences in the potencies to induce endotheliotoxic responses for two structurally similar chemotherapeutics, at a nuclear, cytosolic and membrane levels. Furthermore, our results suggest that the differences in the endothelial toxicities of doxorubicin and daunorubicin are linked to differences in their nuclear accumulation and the DNA damage-triggered response of the endothelium.
Cechy publikacji
peer-reviewed
original-article
Inne
System-identifier
24606
CrossrefMetadata from Crossref logo
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