THE ANTIPROLIFERATIVE EFFECT OF OPIOID RECEPTOR AGONISTS ON THE T47D HUMAN BREAST-CANCER CELL-LINE, IS PARTIALLY MEDIATED THROUGH OPIOID RECEPTORS

In the present study, we investigated the action of opioid receptor ag onists on the proliferation of cells of the T47D human breast cancer c ell line, grown in the absence of exogenously added steroids and growt h factors. We found that the opioid receptor agonists ethylketocyclazo cine, morphine, [D-Ala(2),D-Leu(5)]enkephalin (DADLE), [D-Ser(2),Leu(5 )]enkephalin-Thr(6) (DSLET) and etorphine inhibit dose dependently cel l proliferation. The opioid receptor antagonist diprenorphine had no s ignificant effect per se, but it was able to reverse the action of all opioid receptor agonists except morphine. In order to investigate the mechanism of action of opioids on T47D cells, we characterised the op ioid receptors present on this cell line, by saturation binding, using radiolabelled [D-Ala(2),N-Me-Phe(4)-Gly(5)-ol]enkephalin (DAGO, mu-op ioid receptor agonist), ethylketocyclazocine (kappa(1)-, kappa(2), mu- and delta-opioid receptor agonist), diprenorphine (kappa(2)-, kappa(3 )-, delta- and mu-opioid receptor antagonist), DADLE (delta- and mu-op ioid receptor agonist), and effecters. We identified opioid binding si tes belonging mainly to the kappa-type (kappa(1), kappa(2) and kappa)( 3) a few delta-opioid receptor sites, but no mu-opioid receptors. Our results indicate that the inhibitory effect of opioids on T47D cell gr owth is mediated through kappa- and delta-opioid receptors. The effect of mu-acting morphine might not be mediated through opioid receptors.