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

Abstract

Anthracycline antibiotics are potent anticancer drugs widely used in the treatment of solidtumors and hematological malignancies. Because of their extensive clinical use and their toxiceffect on normal cells, in the present study the effect of these drugs on multipotent hematopoieticbone marrow cells was investigated employing, viability tests, PARP cleavage, Hoechst 33258staining, DNA fragmentation and superoxide anion production techniques. The results revealedthat daunorubicin and doxorubicin exhibited time and dose dependent cytotoxicity againstthe cells and upon increasing the drugs concentrations, apoptosis was occurred after 4 h ofincubation 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 theapoptotic process is PARP dependent. The drugs induced DNA fragmentation and also anionsuperoxide production was increased upon rising drugs concentrations. From the results it isconcluded that anthracycline antibiotics represent cytotoxic effect on hematopoietic progenitor/stem cells of bone marrow, inducing apoptosis and in this process toxicity of daunorubicin ismore pronounced compared to doxorubicin.