Antiproliferative and receptor binding properties of α- and β-casomorphins in the T47D human breast cancer cell line

Abstract

In previous studies, we have shown that opioid agonists ([ d-Ala 2, d-Leu 5]enkephalin (DADLE), [ d-Ser 2,Leu 5]enkephalin-Thr 6 (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 μ-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 α-casein and β-casein), we investigated the antiproliferative action of five different casomorphin peptides: α-casein-(90–95), α-casein-(90–96), β-casomorphin, β-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 δ- and κ-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.