Genotoxic effect of doxorubicin–transferrin conjugate on human leukemia cells
作者： Marzena Szwed , Zofia Jozwiak
DOI: 10.1016/J.MRGENTOX.2014.06.007
关键词:
摘要: Doxorubicin (DOX) is an effective anthracycline antibiotic against a wide spectrum of tumors and hematological malignancies. It mainly interacts with DNA, but can also generate reactive oxygen species (ROS), which damage cell components. Unfortunately, numerous side effects, such as severe cardiotoxicity bone-marrow suppression, limit its use. To reduce this obstacle improve pharmacokinetics, we conjugated DOX to transferrin (TRF), human plasma protein. In our study, compared the effect doxorubicin-transferrin conjugate (DOX-TRF) on leukemic lymphoblasts (CCRF-CEM), normal peripheral blood mononuclear cells (PBMC). parallel, experiments were carried out two chronic myeloid leukemia (CML) lines derived from K562 cells, one was sensitive other resistant doxorubicin (K562/DOX). By use alkaline comet assay, agents induction DNA in determined. Oxidative alkylating assayed by slightly modified assay that included DNA-repair enzymes endonuclease III (Endo III) formamidopyrimidine-DNA glycosylase (Fpg). investigate whether breaks are result apoptosis, examined fragmentation visualized oligosomal ladders after simple agarose electrophoresis under neutral conditions. Modifications genome induced different drugs analyzed following assessment cell-cycle phase. The DOX-TRF caused more than free drug, degree being dependent duration treatment type analyzed. With showed test compounds formation characteristic DNA-ladder pattern. Furthermore, generated higher percentage apoptotic subG1 fraction blocked G2/M phase cycle did DOX. summary, both cancer genotoxic effects apoptosis unconjugated drug.
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