AJP - Regulatory, Integrative and Comparative Physiology, Vol 271, Issue 3 511-R518, Copyright © 1996 by American Physiological Society
Opioid growth factor tonically inhibits human colon cancer cell proliferation in tissue culture
I. S. Zagon, S. D. Hytrek and P. J. McLaughlin
Department of Neuroscience and Anatomy, Pennsylvania State University, College of Medicine, Hershey 17033, USA.
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 12-72 h 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 was
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 (zeta), were found in colon cancer cells by
immunocytochemistry, and receptor binding assays revealed a
nuclear-associated receptor with a dissociation constant of 8.9 nM and a
maximum binding capacity 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 antitumor effect of this peptide in nude mice inoculated with human
colon cancer cells.
