The colon mitosis inhibitor pyroglutamyl-histidyl-glycine inhibits growth of non-tumorigenic colonic epithelial cells.

Abstract

BACKGROUND:

The colon mitosis inhibiting peptide pyroglutamyl-histidyl-glycine (pEHG) increases the expression of c-fos, fosB and egr-1 genes in the colon carcinoma cell line HT-29. However, the effect on non-tumorigenic colonic cells has not been investigated.

MATERIALS AND METHODS:

After exposure of the cell lines YAMC (from colon mucosa of Immorto mice) and IMCE (fromn Immorto-Min mouse hybrid) to pEHG, DNA-synthesis was analysed by H3-thymidine incorporation, apoptosis and necrosis by fluorescence microscopy, and cell cycle distribution by flow cytometry.

RESULTS:

pEHG inhibited DNA-synthesis with a maximal effect at 10(-8)-10(-9) M, but stimulated at 10(-4) M. It blocked cell flow through the cell cycle at GC/M after 8 h of treatment, but had no effect on apoptosis or necrosis at any concentration. A low concentration of ascorbic acid stabilised the cells, maybe as a free radical scavanger.

CONCLUSION:

pEHG inhibits flux at the G2/M transition, but has no effect on cell death.

• Authors: Wenche H Reichelt, Paula M De Angelis, Helle K Knutsen, Trine Husøy, Kjell Elgjo, Karl L Reichelt
• Journal: Anticancer research (Anticancer Res) 2004 Mar-Apr Vol. 24 Issue 2B Pg. 587-91 ISSN: 0250-7005 [Print] Greece
• PMID: 15160998 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Oligopeptides
• Tritium
• pyroglutamyl-histidyl-glycine
• DNA
• Pyrrolidonecarboxylic Acid
• Thymidine

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Cell Death (drug effects, physiology)
• Cell Division (drug effects)
• Cells, Cultured
• Colon (cytology, drug effects)
• DNA (biosynthesis)
• Epithelial Cells (cytology, drug effects)
• Mice
• Mitosis (drug effects)
• Oligopeptides (pharmacology)
• Pyrrolidonecarboxylic Acid (analogs & derivatives)
• Thymidine (metabolism)
• Tritium