Evaluation of Apoptosis in Multipotent Hematopoietic Cells of Bone Marrow by Anthracycline Antibiotics

Document Type: Research article

Authors

1 Department of Biochemistry, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.

2 Department of Bioscience and Biotechnology, Malek-Ashtar University of Technology, Tehran, Iran

3 Department of Biotechnology, Institute of Science and High Technology and Environmental Sciences, Graduate University of Advanced Technology, Kerman, Iran.

Abstract

Anthracycline antibiotics are potent anticancer drugs widely used in the treatment of solid
tumors and hematological malignancies. Because of their extensive clinical use and their toxic
effect on normal cells, in the present study the effect of these drugs on multipotent hematopoietic
bone marrow cells was investigated employing, viability tests, PARP cleavage, Hoechst 33258
staining, DNA fragmentation and superoxide anion production techniques. The results revealed
that daunorubicin and doxorubicin exhibited time and dose dependent cytotoxicity against
the cells and upon increasing the drugs concentrations, apoptosis was occurred after 4 h of
incubation and at low concentration of the drugs. The cleavage of poly ADP-ribose polymerase
(PARP) demonstrated by daunorubicin and doxorubicin treatment of the cells, suggest that the
apoptotic process is PARP dependent. The drugs induced DNA fragmentation and also anion
superoxide production was increased upon rising drugs concentrations. From the results it is
concluded that anthracycline antibiotics represent cytotoxic effect on hematopoietic progenitor/
stem cells of bone marrow, inducing apoptosis and in this process toxicity of daunorubicin is
more pronounced compared to doxorubicin.

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