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

Anticancer Res. 2004 Mar-Apr;24(2B):587-91.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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