Opioid growth factor, [met5]-enkephalin: a tonically active
negative regulator of human colon cancer cell proliferation in tissue
culture.
Zagon, Ian S., Staci D. Hytrek, and Patricia J. McLaughlin.
Departments of Neuroscience and Anatomy and Comparative Medicine,
The Pennsylvania State University, College of Medicine, Hershey,
Pennsylvania 17033
APStracts 3:0094R, 1996.
Native opioid peptides serve as growth factors in a number of normal
and neoplastic cells and tissues, including the prevention and
delayed growth of human colon cancer xenografts in nude mice. This
study examined the hypothesis that opioids exert a direct inhibitory
influence on tumor cell growth by the use of a tissue culture model.
The naturally occurring pentapeptide, [Met5]-enkephalin, depressed
growth of HT-29 human colon cancer cells from 17% to 41% at 12 to 72
hr after administration of 10-6 M concentration; consistent with
previously defined nomenclature, this peptide was termed opioid
growth factor (OGF). OGF action exhibited a dose-response
relationship, was reversible and not cytotoxic, and opioid receptor
mediated. Growth inhibition by OGF was not dependent on serum, and
was noted in the two other human colon cancer cell lines examined:
WiDr and COLO 205. This peptide continually repressed growth because
an increase in cell number was noted when cells were exposed to the
potent opioid antagonist naltrexone or an antibody to OGF. Both OGF
and its receptor, zeta (z), were found in colon cancer cells by
immunocytochemistry, and receptor binding assays revealed a nuclear
associated receptor with a Kd of 8.9 nM and a Bmax of 43 fmol/mg of
protein. OGF was produced and secreted by the tumor cells. These
results lead to the suggestion that OGF has a direct, tonic,
inhibitory action on the growth of human colon cancer cells and
contribute to our understanding of the mechanisms underlying the
marked anti-tumor effect of this peptide in nude mice inoculated with
human colon cancer cells.
Received 8 December 1995; accepted in final form 4 March 1996.
APS Manuscript Number R778-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 20 March 96