Oral trivalent bismuth ions decrease, and trivalent indium or ruthenium ions increase, intestinal tumor burden in...

Immature forms of the peptide hormone gastrin have been implicated in the development of colorectal cancer (CRC). The biological activity of glycine-extended gastrin (Ggly) is dependent on the binding of Fe³⁺ ions in vitro and in vivo. The aim of the present study was to determine the effect of blocking Fe³⁺ ion binding to Ggly, using Bi³⁺, In³⁺ or Ru³⁺ ions, on the development of intestinal tumors in APC^Δ14/+ mice. APC^Δ14/+ mice were treated orally with Bi³⁺, In³⁺ or Ru³⁺ ions for up to 60 days, serum trace metals were analyzed by inductively coupled plasma mass spectrometry, and the incidence and size of intestinal tumors were assessed. Bi³⁺ treatment significantly decreased the number of tumors larger than 3 mm in male mice. In³⁺ or Ru³⁺ treatment significantly increased the tumor burden in all animals and In³⁺ increased the number of tumors larger than 3 mm or 5 mm in male mice alone. The fact that binding of In³⁺ or Ru³⁺ ions to Ggly was orders of magnitude stronger than the binding of Bi³⁺ ions implies that the inhibitory effect of Bi³⁺ ions is not a consequence of a reduction in Ggly activity. However, further testing of higher doses of Bi³⁺ ions for longer periods as an oral treatment for intestinal tumors is warranted.