Free radical production and labile iron pool decrease triggered by subtoxic concentration of aclarubicin in human leukemia cell lines

Abstract 

Aclarubicin (ACLA), which belongs to the antracycline class of antineoplasic agents, has been demonstrated as a differentiating agent for a broad range of human solid tumors and leukemia. By using dihydroethidium as a fluorescent probe, we show the ability of subtoxic (i.e. differentiating) concentration of ACLA to generate reactive oxygen species in both K562 and HL-60 leukemia cell lines. Besides, we have used a calcein-based spectrofluorimetric assay to determine the influence of ACLA treatment on the cellular labile iron pool (LIP). In both cell lines, the LIP level was markedly decreased in the presence of ACLA. Nevertheless, whereas ACLA-induced differentiation was obviously ROS-dependent, the LIP decrease was rather ROS-independent.

Abbreviations: ACLA, aclarubicin, Calcein-AM, calcein-acetoxy-methyl-ester, IRE, iron responsive element, IRP, iron regulatory protein, LIP, labile iron pool, NAC, N-acetylcysteine, NBT, nitroblue-tetrazolium, PDTC, pyrrolidone-dithiocarbamate, ROS, reactive oxygen species

Keywords: Aclarubicin, Differentiation, HL-60, K562, Labile iron pool, Oxidative stress