Document Detail

Opioids and the apoptotic pathway in human cancer cells.
MedLine Citation:
PMID:  12747939     Owner:  NLM     Status:  MEDLINE    
This study was designed to examine the role of opioids in cell survival, with an emphasis on the mechanism of opioid growth factor (OGF, [Met(5)]-enkephalin)-dependent growth inhibition. Using three human cancer cell lines: MIA PaCa-2 pancreatic adenocarcinoma, HT-29 colon adenocarcinoma, and CAL-27 squamous cell carcinoma of the head and neck, and OGF and the opioid antagonist naltrexone (NTX) at a dosage (10(-6)M) selected because it is known to repress or increase, respectively, cell replication, the effects on apoptosis (TUNEL, Annexin V) and necrosis (trypan blue) were investigated on days 2, 5, and 7 of exposure. In addition, the influence of a variety of other natural and synthetic opioids on apoptosis and necrosis was examined at a dosage of 10(-6)M. OGF, NTX, naloxone, [D-Pen(2,5)]-enkephalin, [Leu(5)]-enkephalin, dynorphin A1-8, beta-endorphin, endomorphin-1 and -2, and methadone at concentrations of 10(-6)M did not alter cell viability of any cancer cell line. Exposure of cultures to [D-Ala(2),MePhe(4),Glycol(5)]-enkephalin (DAMGO), morphine, or etorphine at 10(-6)M significantly increased the number of adherent cells positively stained for TUNEL and Annexin V, as well as the number of necrotic cells in the supernatant, from control levels at all time points studied. The effects of DAMGO, morphine, and etorphine on apoptosis/necrosis were not fully blocked by concomitant administration of naloxone. Despite the increase in cell death in some opioid-treated groups, the number of apoptotic and necrotic adherent cells, and the number of necrotic cells in the supernatant, was no more than 1-2% of the total cell population. These results indicate that the inhibitory (OGF) or stimulatory (NTX) action on cell growth in tissue culture is not due to alterations in apoptotic or necrotic pathways. Moreover, although some opioids increased cell death, and dose-effect relationships need to be established, this activity was not of great magnitude and supports the previously reported lack of growth inhibition of many of these compounds.
Ian S Zagon; Patricia J McLaughlin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Neuropeptides     Volume:  37     ISSN:  0143-4179     ISO Abbreviation:  Neuropeptides     Publication Date:  2003 Apr 
Date Detail:
Created Date:  2003-05-15     Completed Date:  2003-07-14     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8103156     Medline TA:  Neuropeptides     Country:  Scotland    
Other Details:
Languages:  eng     Pagination:  79-88     Citation Subset:  IM    
Department of Neuroscience and Anatomy, The Milton S. Hershey Medical Center, The Pennsylvania State University, College of Medicine, 500 University Drive, H-109, Hershey, PA 17033, USA.
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MeSH Terms
Annexin A5 / metabolism
Apoptosis / drug effects*
Cell Adhesion / drug effects
Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / pharmacology
Etorphine / pharmacology
Growth Substances / pharmacology
In Situ Nick-End Labeling
Morphine / pharmacology
Naltrexone / pharmacology
Narcotic Antagonists / pharmacology
Narcotics / pharmacology*
Neoplasms / pathology*
Tumor Cells, Cultured
Reg. No./Substance:
0/Annexin A5; 0/Growth Substances; 0/Narcotic Antagonists; 0/Narcotics; 100929-53-1/Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; 14521-96-1/Etorphine; 16590-41-3/Naltrexone; 57-27-2/Morphine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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