Antiproliferative and receptor binding properties of alpha- and beta-casomorphins in the T47D human breast cancer cell line.

Abstract

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.

• Authors: A Hatzoglou, E Bakogeorgou, C Hatzoglou, P M Martin, E Castanas
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 310 Issue 2-3 Pg. 217-23 (Aug 29 1996) ISSN: 0014-2999 [Print] Netherlands
• PMID: 8884220 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Caseins
• Receptors, Somatostatin

Topics

• Breast Neoplasms (metabolism, pathology)
• Caseins (metabolism, pharmacology)
• Cell Division (drug effects)
• Humans
• Protein Binding
• Receptors, Somatostatin (metabolism)
• Tumor Cells, Cultured