Related Experiment Videos
Endogenous opioids and the growth regulation of a neural tumor
1Department of Anatomy, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.
Abstract:
Endogenous opioid systems (endogenous opioids and their receptors) are known to participate in the regulation of tumor growth. The present study was conducted to examine whether [Met5]-enkephalin influences the growth of transplanted neuroblastoma, and to explore the role of other opioid peptides in carcinogenesis. A/Jax mice were inoculated with 10(6) S20Y cells and received daily injections of [Met5]-enkephalin. Dosages of 0.5 to 30 mg/kg delayed tumor appearance and prolonged survival of these mice; antitumor effects were blocked by concomitant injections of naloxone. Daily administration (10 mg/kg) of [Leu5]-enkephalin had no effect on neurotumor growth. [D-Ala2, D-Leu5]-enkephalin and ethylketocyclazocine, ligands selective for delta and kappa receptors, respectively, also did not influence neuro-oncogenesis. These results demonstrated the potent growth inhibiting effects of the naturally occurring opioid pentapeptide, [Met5]-enkephalin, and substantiate reports identifying and characterizing an opioid receptor (i.e., zeta) for which [Met5]-enkephalin is the most potent ligand.
Insights
The opioid peptide [Met5]-enkephalin inhibits neuroblastoma growth in mice. This antitumor effect, mediated by a specific opioid receptor, highlights the role of endogenous opioids in cancer regulation.
Area of Science:
- Oncology
- Neuroscience
- Pharmacology
Background:
- Endogenous opioid systems modulate tumor growth.
- The specific role of [Met5]-enkephalin in carcinogenesis requires further investigation.
Purpose of the Study:
- To determine the effect of [Met5]-enkephalin on transplanted neuroblastoma growth.
- To explore the involvement of other opioid peptides and receptors in neuro-oncogenesis.
Main Methods:
- Transplanted neuroblastoma (S20Y cells) in A/Jax mice.
- Daily injections of [Met5]-enkephalin at varying dosages.
- Co-administration with naloxone and administration of other opioid peptides ([Leu5]-enkephalin, [D-Ala2, D-Leu5]-enkephalin) and ethylketocyclazocine.
Main Results:
- [Met5]-enkephalin significantly delayed tumor appearance and prolonged survival.
- Antitumor effects were reversed by naloxone.
- [Leu5]-enkephalin, delta-selective, and kappa-selective ligands showed no impact on tumor growth.
Conclusions:
- Naturally occurring [Met5]-enkephalin exhibits potent growth-inhibiting effects on neuroblastoma.
- These findings support the existence of a zeta opioid receptor, with [Met5]-enkephalin as its most potent ligand.