title: The antiproliferative effect of opioid receptor agonists on the T47D human breast cancer cell line, is partially mediated through opioid receptors.
abstract: In the present study, we investigated the action of opioid receptor agonists on the proliferation of cells of the T47D human breast cancer cell line, grown in the absence of exogenously added steroids and growth factors. We found that the opioid receptor agonists ethylketocyclazocine, morphine, [D-Ala2,D-Leu5]enkephalin (DADLE), [D-Ser2,Leu5]enkephalin-Thr6 (DSLET) and etorphine inhibit dose dependently cell proliferation. The opioid receptor antagonist diprenorphine had no significant 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 opioid receptors present on this cell line, by saturation binding, using radiolabelled [D-Ala2,N-Me-Phe4-Gly5-ol]enkephalin (DAGO, mu-opioid 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-opioid receptor agonist), and effectors. We identified opioid binding sites 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 growth is mediated through kappa- and delta-opioid receptors. The effect of mu-acting morphine might not be mediated through opioid receptors.
authors.affiliation: Laboratory of Experimental Endocrinology, University of Crete, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Hatzoglou
authors.forename: E
authors.initials: E
authors.lastname: Bakogeorgou
authors.forename: E
authors.initials: E
authors.lastname: Castanas
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000595:Amino Acid Sequence; D001665:Binding Sites; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D016308:Enkephalin, Leucine-2-Alanine / Q000494:pharmacology; D004745:Enkephalins / Q000494:pharmacology; D016314:Ethylketocyclazocine / Q000494:pharmacology; D005048:Etorphine / Q000494:pharmacology; D006801:Humans; D008969:Molecular Sequence Data; D009020:Morphine / Q000494:pharmacology; D009292:Narcotic Antagonists; D018847:Opioid Peptides / Q000378:metabolism; D011957:Receptors, Opioid / Q000819:agonists* / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D004745:Enkephalins; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D011957:Receptors, Opioid; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D005048:Etorphine; D016314:Ethylketocyclazocine; D004743:Enkephalin, Leucine; D016308:Enkephalin, Leucine-2-Alanine; C034318:enkephalin, Ser(2), Leu(5), Thr(6)-; D009020:Morphine