Endogenous opioids and the growth regulation of a neural tumor

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 10⁶ 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.