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.