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

Area of Science:

• Oncology
• Gastroenterology
• Biochemistry

Background:

• Immature gastrin peptides are linked to colorectal cancer (CRC) development.
• Glycine-extended gastrin (Ggly) activity relies on iron (Fe3+) ion binding.
• Targeting Fe3+ binding to Ggly may offer a novel therapeutic strategy for CRC.

Purpose of the Study:

• To investigate the impact of blocking Fe3+ binding to Ggly using Bismuth (Bi3+), Indium (In3+), or Ruthenium (Ru3+) ions.
• To assess the effects of these ions on intestinal tumor development in APCΔ14/+ mouse models.

Main Methods:

• APCΔ14/+ mice were orally administered Bi3+, In3+, or Ru3+ ions for up to 60 days.
• Serum trace metal levels were quantified using inductively coupled plasma mass spectrometry.
• Intestinal tumor incidence and size were evaluated.

Main Results:

• Bi3+ treatment significantly reduced the number of intestinal tumors larger than 3 mm in male mice.
• In3+ and Ru3+ treatments increased overall tumor burden in all mice.
• In3+ specifically elevated the count of tumors exceeding 3 mm or 5 mm in male mice.

Conclusions:

• The differential effects of Bi3+, In3+, and Ru3+ suggest complex interactions with Ggly and tumor development.
• The inhibitory effect of Bi3+ is unlikely due to reduced Ggly activity, given stronger binding of In3+/Ru3+.
• Further investigation of higher Bi3+ doses and extended treatment durations for intestinal tumors is warranted.