Increased proapoptotic activity of electron beam irradiated doxorubicin and epirubicin in multidrug-resistant human leukemic cells.
PBN-AR
Instytucja
Sieć Badawcza Łukasiewicz - Instytut Biotechnologii i Antybiotyków
Informacje podstawowe
Główny język publikacji
en
Czasopismo
CHEMICO-BIOLOGICAL INTERACTIONS
ISSN
0009-2797
EISSN
Wydawca
ELSEVIER IRELAND LTD
DOI
URL
Rok publikacji
2016
Numer zeszytu
258
Strony od-do
69-78
Numer tomu
Identyfikator DOI
Liczba arkuszy
Słowa kluczowe
angielski
Anthracyclines
Electron beam irradiation
Multidrug resistance
Apoptosis
Acute lymphoblastic leukemia
Streszczenia
Język
angielski
Treść
This study evaluated the effect of electron beam irradiation on the cytotoxic activity of anthracycline antibiotics such as doxorubicin (DOX), epirubicin (EPI), and dunorubicin (DAU) in human acute lymphoblastic leukemia cell line CCRF-CEM and its multidrug-resistant variant CCRF-VCR1000 cell line characterized by the overexpression of ABCB1 gene. Drugs were irradiated at doses of 10 and 25 kGy. Data from EPR studies proved that the highest concentration of free radicals was found in DOX and that the number of stable free radicals is always greater after irradiation. In in vitro studies, a higher cytotoxic activity of irradiated DOX and EPI in multidrug-resistant CCRF-VCR1000 cells was observed. This tendency was maintained during the storage at 4 C for 90 days. Changes in CCRF-CEM cells' viability were not dependent on the irradiation status and its dose and were only drug-concentration dependent in all measurement time points. It was proved that increased potency of 25 kGy e-beam irradiated drugs results from their enhanced proapoptotic activity. Apoptotic cell death observed in CCRF-VCR1000 cells treated with irradiated drugs was caspase-8, -9, and -3 dependent and related to the increased Bax/Bcl-2 ratio. No significant differences in the effects of irradiated and non-irradiated drugs on p53 and NFkB transcription factor level and their translocation to the nucleus were noted. Increased activity of the irradiated drugs was not dependent on ABCB1 level.
Inne
System-identifier
PX-5898677582cecc3cf9292423
CrossrefMetadata from Crossref logo
Cytowania
Liczba prac cytujących tę pracę
Brak danych
Referencje
Liczba prac cytowanych przez tę pracę
Brak danych