Antiproliferative and receptor binding properties of alpha- and beta-casomorphins in the T47D human breast cancer cell line.
In previous studies, we have shown that opioid agonists ([D-Ala2, D-Leu5]enkephalin (DADLE), [D-Ser2, Leu5]enkephalin-Thr6 (DSLET), ethylketocyclazocine and etorphine) bind to opioid binding sites and decrease cell proliferation of human T47D breast cancer cells. Furthermore, we provided evidence about a cross-reaction, also in the T47D human breast cancer cell line, of mu-acting opioids with type-II somatostatin receptors. Since a potential source of opioid activity in the breast might be casomorphin peptides (produced by the enzymatic degradation of alpha-casein and beta-casein), we investigated the antiproliferative action of five different casomorphin peptides: alpha-casein-(90-95), alpha-casein-(90-96), beta-casomorphin, beta-casomorphin-(1-5) and morphiceptin. We show that all five peptides decreased, in a dose-dependent manner, cell proliferation. The general antagonist diprenorphine produced only a partial reversal of their action. Furthermore, we provide evidence that all peptides (except for morphiceptin) bind to delta- and kappa-opioid binding sites of T47D cells with different selectivity. Finally, we show that these peptides are also partial competitors at the somatostatin receptors present in the same cell line.
Hatzoglou
A
A
Laboratory of Experimental Endocrinology, University of Crete School of Medicine, Heraklion, Greece.
Bakogeorgou
E
E
Hatzoglou
C
C
Martin
P M
PM
Castanas
E
E
D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002364:Caseins / Q000378:metabolism / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D011485:Protein Binding; D017481:Receptors, Somatostatin / Q000378:metabolism; D014407:Tumor Cells, Cultured
D002364:Caseins; D017481:Receptors, Somatostatin