Figure 7 Effect of iron chelators on cellular localization of TfR1, ferritin-H customer reviews and FPN in oesophageal-derived xenografts. Immunohistochemistry was performed on xenografts derived from OE33 (A), OE19 (B) and OE21 (C) in vehicle- or deferasirox-treated mice to assess … Discussion and conclusions Mounting evidence supports a role for iron chelators in the treatment of cancer (Richardson, 2002; Whitnall et al., 2006; Yu et al., 2006; Richardson et al., 2009; Kovacevic et al., 2011; Merlot et al., 2012). However, many of these studies are based on experimental iron chelators that are at the preclinical stage and are not approved for clinical use. Another approach is to use existing licensed iron chelators, commonly used for the treatment of patients with iron overload disease.

One such chelator, DFO, has shown promise in clinical trials (Estrov et al., 1987; Donfrancesco et al., 1990; 1992; 1995). However, the major drawback of DFO in clinical practice is the requirement for continuous subcutaneous infusions related to its short half-life and hydrophilic nature (Merlot et al., 2012). An alternative is the licensed oral iron chelator, deferasirox, which has a half-life of 7�C18 h and is administered once daily (Lindsey and Olin, 2007). However, little data are available assessing this drug as an anti-cancer agent (Chantrel-Groussard et al., 2006; Lescoat et al., 2007; Cappellini, 2008; Ohyashiki et al., 2009; Messa et al., 2010; Fukushima et al., 2011). The current study is the first to provide evidence that deferasirox may be of use in oesophageal cancer treatment.

Deferasirox (like DFO) can act as an iron chelator in oesophageal cancer cell models and is able to both inhibit iron uptake and mobilize iron from cells. The resulting decrease in cellular iron in oesophageal cancer cells is reflected by increased TfR1 expression, consistent with classical IRP theory and previous studies examining iron chelators as anti-cancer agents (Whitnall et al., 2006; Muckenthaler et al., 2008). Reduced cellular iron is likely, in part, to account for the anti-proliferative effect of these ligands against oesophageal cancer cells. In fact, both DFO and deferasirox are able to ablate iron-mediated pro-proliferative responses (Boult et al., 2008). Importantly, these in vitro effects were observed across all three oesophageal cell lines, suggesting the effect of modulating cellular iron levels is not cell lineage dependent. This is consistent with existing literature using experimental Dacomitinib chelators (Richardson, 2002; Whitnall et al., 2006; Yu et al., 2006; Richardson et al., 2009; Kovacevic et al., 2011; Merlot et al., 2012). Additionally, we assessed the ability of deferasirox to inhibit tumour growth in vivo using a murine xenograft model.