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


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.


CONCLUSIONS
pEHG inhibits flux at the G2/M transition, but has no effect on cell death.
Reichelt
Wenche H
WH
Institute of Pediatric Research, University of Oslo, The National Hospital, NO-0027 Oslo, Norway. w.h.reichelt@klinmed.uio.no
De Angelis
Paula M
PM
Knutsen
Helle K
HK
Husøy
Trine
T
Elgjo
Kjell
K
Reichelt
Karl L
KL
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003106:Colon / Q000166:cytology / Q000187:drug effects*; D004247:DNA / Q000096:biosynthesis; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008938:Mitosis / Q000187:drug effects*; D009842:Oligopeptides / Q000494:pharmacology*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D000970:Antineoplastic Agents; D009842:Oligopeptides; D014316:Tritium; C023866:pyroglutamyl-histidyl-glycine; D004247:DNA; D011761:Pyrrolidonecarboxylic Acid; D013936:Thymidine