Deferasirox (ICL670A) effectively inhibits oesophageal cancer growth
in vitro and in vivo
S J Ford1, P Obeidy2, D B Lovejoy2, M Bedford1, L Nichols1, C
Chadwick1, O Tucker1, G Y L Lui2,
D S Kalinowski2, P J Jansson2, T H Iqbal1, D Alderson1, D R
Richardson2,*, C Tselepis1,
British Journal of Pharmacology

Background and purpose
Growing evidence implicates iron in the aetiology of gastrointestinal
cancer. Furthermore, studies demonstrate that iron chelators possess
potent anti-tumour activity, although whether iron chelators show
activity against oesophageal cancer is not known.
Experimental approach
The effect of the iron chelators, deferoxamine (DFO) and deferasirox,
on cellular iron metabolism, viability and proliferation was assessed
in two oesophageal adenocarcinoma cell lines, OE33 and OE19, and the
squamous oesophageal cell line, OE21. A murine xenograft model was
employed to assess the effect of deferasirox on oesophageal tumour
burden. The ability of chelators to overcome chemo-resistance and to
enhance the efficacy of standard chemotherapeutic agents (cisplatin,
fluorouracil and epirubicin) was also assessed.
Key results
Deferasirox and DFO effectively inhibited cellular iron acquisition
and promoted intracellular iron mobilisation. The resulting reduction
in cellular iron levels was reflected by increased transferrin
receptor 1 expression and reduced cellular viability and
proliferation. Treating oesophageal tumour cell lines with an iron
chelator in addition to a standard chemotherapeutic agent resulted in
a reduction in cellular viability and proliferation compared to the
chemotherapeutic agent alone. Both DFO and deferasirox were able to
overcome cisplatin-resistance. Furthermore, in human xenograft models,
deferasirox was able to significantly suppress tumour growth which was
associated with decreased tumour iron levels.
Conclusions and implications
The clinically established iron chelators, DFO and deferasirox,
effectively deplete iron from oesophageal tumour cells, resulting in
growth suppression. These data provide a platform for assessing the
utility of these chelators in the treatment of oesophageal cancer

Keywords:Oesophageal cancer;iron chelation;cancer;deferasirox

*DOI: 10.1111/bph.12045

© 2012 The Authors. British Journal of Pharmacology © 2012 The British
Pharmacological Society


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