Oral trivalent bismuth ions decrease, and trivalent indium or ruthenium ions increase, intestinal tumor burden in ApcΔ14/+ mice

Metallomics. 2018 Jan 24;10(1):194-200. doi: 10.1039/c7mt00272f.

Abstract

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 APCΔ14/+ mice. APCΔ14/+ 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenomatous Polyposis Coli Protein / genetics
  • Adenomatous Polyposis Coli Protein / metabolism
  • Animals
  • Bismuth / chemistry
  • Bismuth / pharmacology*
  • Exons
  • Hematologic Tests
  • Indium / chemistry
  • Indium / toxicity*
  • Intestinal Neoplasms / chemically induced*
  • Intestinal Neoplasms / drug therapy*
  • Intestinal Neoplasms / pathology
  • Mice
  • Mice, Inbred C57BL
  • Point Mutation
  • Ruthenium / chemistry
  • Ruthenium / toxicity*
  • Tumor Burden

Substances

  • Adenomatous Polyposis Coli Protein
  • adenomatous polyposis coli protein, mouse
  • Indium
  • Ruthenium
  • Bismuth