An endogenous colon mitosis inhibitor reduces proliferation of colon carcinoma cells (HT 29) in serum-restricted medium
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1Institute of Pathology, Rikshospitalet, Oslo, Norway.
Abstract:
Extracts of mouse intestine contain a colonic epithelial mitosis inhibitor that has recently been purified and identified as a tripeptide (pGlu-His-GlyOH). In order to elucidate further the biological characteristics of this peptide, the effect of the tripeptide on cell proliferation in a human colon carcinoma cell line (HT 29) was examined. The incorporation of tritiated thymidine was significantly reduced at 20-30 h after addition of the tripeptide. The dose-response relationship was bell-shaped with loss of inhibitory effect at high or low doses. The number of cells were significantly reduced at a peptide concentration of 10(-8) M at 24 h, but not at 48 or 72 h after addition of the peptide. The inhibition was reversible, and was only observed when the cells were grown in a serum-restricted medium (1%). The inhibitory effect was abolished by increasing the serum content to 10% or adding insulin to the medium.
Insights
A novel tripeptide (pGlu-His-GlyOH) inhibits colon cancer cell proliferation. This colon mitosis inhibitor
Area of Science:
- Gastroenterology
- Molecular Biology
- Oncology
Background:
- Mouse intestine extracts contain a colonic epithelial mitosis inhibitor.
- The inhibitor was purified and identified as a tripeptide: pGlu-His-GlyOH.
Purpose of the Study:
- To investigate the biological characteristics of the tripeptide.
- To examine the effect of the tripeptide on human colon carcinoma cell line (HT 29) proliferation.
Main Methods:
- Assessing tritiated thymidine incorporation in HT 29 cells.
- Evaluating cell numbers at various time points and peptide concentrations.
- Testing the effect of serum concentration and insulin addition.
Main Results:
- The tripeptide significantly reduced thymidine incorporation at 20-30 hours.
- A bell-shaped dose-response curve was observed, with inhibition lost at extreme doses.
- Cell numbers decreased at 10(-8) M peptide concentration within 24 hours.
- Inhibition was reversible and dependent on low serum conditions (1%), abolished by 10% serum or insulin.
Conclusions:
- The tripeptide (pGlu-His-GlyOH) exhibits cell cycle inhibitory properties in colon cancer cells.
- Its efficacy is context-dependent, requiring specific serum concentrations for optimal activity.
- This peptide represents a potential therapeutic agent for colon cancer, warranting further investigation.