Molecular damage caused by generation of reactive oxygen species in the redox cycle of doxorubicin–transferrin conjugate in human leukemia cell lines

Abstract

In this study we focused on evaluation of the pro-oxidant properties of doxorubicin–transferrin (DOX-TRF) conjugate and its potency to damage macromolecules which are components of cellular compartments. Our experiments were performed on two human leukemia cell lines: K562 (chronic erythromyeloblastoid leukemia) and CCRF-CEM (acute lymphoblastic leukemia). We determined the reactive oxygen species (ROS) production and programmed cell death (PCD) induction by free DOX and its conjugate. Besides this, the lipid peroxidation and protein damage which can be provoked by DOX alone and DOX-TRF conjugate were assessed. ROS were produced in leukemia cells incubated with free DOX and DOX-TRF conjugate and the extent of apoptosis and necrosis was strongly dependent on the cell line, sensitivity to drug and time of incubation with the investigated compounds. The role of ROS in DOX-TRF conjugate-induced cell death was confirmed by the diminution effects of the antioxidant vitamin C.

Keywords::

• Drug resistance
• pharmacotherapeutics
• signal transduction

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.

This work was supported in part by Grant no. 505/756 of the University of Lodz, Poland.