TY - JOUR
T1 - Endogenous opioid systems regulate growth of neural tumor cells in culture
AU - Zagon, Ian S.
AU - McLaughlin, Patricia J.
N1 - Funding Information:
This research was supported by NIH Grants NS-20623 and NS-20500. We are grateful to Laura Nagy and Susan Pileggi for technical assistance, and to Exon-Intron, Inc. (Washington, DC) for the human fibrosarcoma cell line.
PY - 1989/6/19
Y1 - 1989/6/19
N2 - Endogenous opioid systems (i.e., opioids and opioid receptors) play a role in neural cancer. Using a tissue culture system of S20Y murine neuroblastoma to assess the effects of opioids on growth, [Met5]-enkephalin was the most potent compound to influence cell replication. With a median effective concentration of 10-10 M, this peptide inhibited cell proliferation in a stereospecific and naloxone-reversible manner. [Met5]-Enkephalin depressed both DNA synthesis and mitosis. [Met5]-Enkephalin was detected in neuroblastoma cells by radioimmunoassay, and was found to increase in concentration in culture media over time, suggesting that these cells produced the peptide. Immunocytochemistry showed [Met5]-enkephalin-like activity in the cortical cytoplasm, but not the cell nucleus, of neuroblastoma cells. Binding of [3H]-[Met5]-enkephalin was specific and saturable, and Scatchard analysis yielded a Kd of 1.2 ± 0.1 nM and a binding capacity of 50.2 ± 4.3 fmol/mg protein. [Met5]-Enkephalin also depressed the growth of N115 murine neuroblastoma, SK-N-MC human neuroblastoma, and HT-1080 human fibrosarcoma. These results indicate that [Met5]-enkephalin, a naturally occurring pentapeptide that is derived from proenkephalin A, is a potent inhibitor of cell growth. Since cancer cells produce [Met5]-enkephalin, and contain a binding site to this ligand, endogenous opioid systems appear to control cell proliferation by an autocrine mechanism.
AB - Endogenous opioid systems (i.e., opioids and opioid receptors) play a role in neural cancer. Using a tissue culture system of S20Y murine neuroblastoma to assess the effects of opioids on growth, [Met5]-enkephalin was the most potent compound to influence cell replication. With a median effective concentration of 10-10 M, this peptide inhibited cell proliferation in a stereospecific and naloxone-reversible manner. [Met5]-Enkephalin depressed both DNA synthesis and mitosis. [Met5]-Enkephalin was detected in neuroblastoma cells by radioimmunoassay, and was found to increase in concentration in culture media over time, suggesting that these cells produced the peptide. Immunocytochemistry showed [Met5]-enkephalin-like activity in the cortical cytoplasm, but not the cell nucleus, of neuroblastoma cells. Binding of [3H]-[Met5]-enkephalin was specific and saturable, and Scatchard analysis yielded a Kd of 1.2 ± 0.1 nM and a binding capacity of 50.2 ± 4.3 fmol/mg protein. [Met5]-Enkephalin also depressed the growth of N115 murine neuroblastoma, SK-N-MC human neuroblastoma, and HT-1080 human fibrosarcoma. These results indicate that [Met5]-enkephalin, a naturally occurring pentapeptide that is derived from proenkephalin A, is a potent inhibitor of cell growth. Since cancer cells produce [Met5]-enkephalin, and contain a binding site to this ligand, endogenous opioid systems appear to control cell proliferation by an autocrine mechanism.
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U2 - 10.1016/0006-8993(89)90425-3
DO - 10.1016/0006-8993(89)90425-3
M3 - Article
C2 - 2758319
AN - SCOPUS:0024327163
SN - 0006-8993
VL - 490
SP - 14
EP - 25
JO - Brain research
JF - Brain research
IS - 1
ER -