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The induction of apoptosis by daunorubicin and idarubicin in human trisomic and diabetic fibroblasts

Abstract

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 timedependent 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.

Abbreviations

DiOC6(3):

3,3′-dihexyloxycarbocyanin iodide

DNR:

daunorubicin

DS:

Down’s syndrome

IC50 :

the drug concentration that reduces cell growth to 50% of that of the control cells

IDA:

idarubicin

MTT:

3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide

PBS:

phosphate buffered saline

Z-(DEVD-AMC):

Z-(Asp-Glu-Val-Asp)-7-amido-4-methylcoumarin

ΔΨm :

mitochondrial membrane potential

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Correspondence to Zofia Jóźwiak.

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Dragojew, S., Marczak, A., Maszewski, J. et al. The induction of apoptosis by daunorubicin and idarubicin in human trisomic and diabetic fibroblasts. Cell Mol Biol Lett 13, 182–194 (2008). https://doi.org/10.2478/s11658-007-0045-7

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  • DOI: https://doi.org/10.2478/s11658-007-0045-7

Key words

  • Daunorubicin
  • Idarubicin
  • Apoptosis
  • Fibroblasts
  • Down’s syndrome
  • Diabetes