Effects of Deferoxamine on Leukemia In Vitro and Its Related Mechanism

Abstract

BackgroundThis study aimed to investigate the effect of deferoxamine (DFO) on leukemia in vitro, and to explore the underlying molecular mechanism.Material/MethodsK562 leukemia cells were treated with various concentrations of DFO (10, 50, and 100 μmol/l) with or without 10 μmol/l ferric chloride for 12 h. Then, total cellular iron was detected. CCK-8 kit and flow cytometry were used for cell viability and apoptosis detection. In addition, expression of apoptosis-related genes was determined by Western blotting and qRT-PCR, respectively.ResultsThe results suggested that DFO significantly inhibited K562 cell viability and induced cell apoptosis in a dose-dependent manner. We also found that the protein and mRNA levels of Bax, p53, and Fas dose-dependently increased in DFO-treated K562 cells, while the level of Bcl-2 markedly decreased in a dose-dependent manner. Moreover, the findings showed that ferric chloride eliminated these effects on K562 cells caused by DFO treatment.ConclusionsOur results indicate that DFO plays a protective role in leukemia via inhibiting leukemia cell viability and inducing cell apoptosis by the regulation of apoptosis-related genes expression.

Iron chelation cancer therapy using hydrophilic block copolymers conjugated with deferoxamine

“…Many previous studies reported that iron deprivation has a great potential in cancer treatment in in vitro conditions, 6,11‐15 and DFO has been most extensively investigated as the efficient iron chelator because of its excellent iron‐selectivity and safety 7,10 . However, only a few studies have demonstrated its in vivo therapeutic efficiency probably due to its poor biodistribution.…”

“…In addition, the hexadentate ligand prevents Fe(III) from producing hydroxy radicals via Fenton reaction, 7,9,10 which may contribute to avoidance of untoward toxicity. Previous studies have demonstrated that numerous cancer cell lines are sensitive to iron depletion by DFO 6,11‐15 . In addition, several clinical studies have shown that DFO exhibits antitumor activity in patients with neuroblastoma, leukemia, and hepatocellular carcinoma 16‐18 .…”

“…Cancer cells have high iron requirements due to their rapid growth and proliferation, and iron overload has been reported to promote oncogenesis and tumor growth 1,2 . In this context, iron depletion using iron chelators has been reported to inhibit cancer cell proliferation by inducing cell cycle arrest and apoptosis 3‐6 . In particular, deferoxamine (DFO), which is the widely used iron chelator for iron overload disease, has attracted much attention in cancer treatment because of the safety profiles approved by the US FDA.…”

“…1,2 In this context, iron depletion using iron chelators has been reported to inhibit cancer cell proliferation by inducing cell cycle arrest and apoptosis. [3][4][5][6] In particular, deferoxamine (DFO), which is the widely used iron chelator for iron overload disease, has attracted much attention in cancer treatment because of the safety profiles approved by the US FDA. Due to its hexadentate has limited the therapeutic potential and practical application.…”

Prognostic Biomarkers for Predicting Papillary Thyroid Carcinoma Patients at High Risk Using Nine Genes of Apoptotic Pathway

“…Various studies have confirmed that diminishing iron content inhibits tumor cell proliferation and induces apoptosis (54,55). Out of the various iron-chelators available, DFO is the most widely used iron-chelator and has shown to display these anti-tumor effects (56,57).…”