Involvement of reactive oxygen species in aclarubicin-induced death of human trisomic and diabetic fibroblasts.
We investigated the mode of cell death induced by aclarubicin in human trisomic and diabetic fibroblasts. The cells were incubated with aclarubicin for 2 h and then were cultured in drug-free medium for up to 96 h. Aclarubicin in trisomic and diabetic fibroblasts, compared with normal cells, induced lesser changes in the level of reactive oxygen species (ROS) and the content of intracellular calcium. The drug induced ROS-mediated apoptotic and necrotic pathways in all cell lines. The extent of apoptosis and necrosis was strongly dependent on the cell line, sensitivity to drug and post-treatment time. These results indicate that most resistant diabetic cells died prevalently by apoptosis. In the case of trisomic fibroblasts, the number of apoptotic cells decreased with post-incubation time. The role of reactive oxygen species in aclarubicin-induced cell death was confirmed by the diminution effects of antioxidants (N-acetylcysteine and pyrrolidine-dithiocarbamate) on drug-induced ROS formation, increase of intracellular calcium and the extent of apoptosis and necrosis in fibroblast cell lines.
Kania
Katarzyna
K
Department of Thermobiology, University of Łódź, 12/16 Banacha St., 90-237 Łódź, Poland.
Zych
Aneta
A
Jóźwiak
Zofia
Z
D000111:Acetylcysteine / Q000494:pharmacology; D015250:Aclarubicin / Q000633:toxicity*; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004314:Down Syndrome / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005347:Fibroblasts / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009336:Necrosis / Q000188:drug therapy; D011759:Pyrrolidines / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013859:Thiocarbamates / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D011759:Pyrrolidines; D017382:Reactive Oxygen Species; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D015250:Aclarubicin; D002118:Calcium; D000111:Acetylcysteine