The induction of apoptosis by daunorubicin and idarubicin in human trisomic and diabetic fibroblasts.
In this study, we investigated apoptosis induced in human trisomic and diabetic fibroblasts by daunorubicin (DNR) and its derivative, idarubicin (IDA). The cells were incubated with DNR or IDA for 2 h and then cultured in a drug-free medium for a further 2-48 h. The apoptosis in the cultured cell lines was assessed by biochemical analysis. We found that both drugs induced a time dependent loss of mitochondrial membrane potential, and a significant increase in intracellular calcium and caspase-3 activity. Mitochondrial polarization and changes in the level of intracellular calcium were observed during the first 2-6 h after drug treatment. Caspase-3 activation occurred in the late stages of the apoptotic pathway. Our findings also demonstrated that idarubicin was more cytotoxic and more effective than daunorubicin in inducing apoptosis in trisomic and diabetic fibroblasts.
Dragojew
Sylwia
S
Department of Thermobiology, University of Łódź, Banacha 12/16, 90-237, Łódź, Poland.
Marczak
Agnieszka
A
Maszewski
Janusz
J
Ilnicki
Krzysztof
K
Jóźwiak
Zofia
Z
D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D003630:Daunorubicin / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000473:pathology*; D004789:Enzyme Activation / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology*; D006801:Humans; D015255:Idarubicin / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D014314:Trisomy / Q000473:pathology*
D053148:Caspase 3; D002118:Calcium; D015255:Idarubicin; D003630:Daunorubicin