OPIOID ALKALOIDS AND CASOMORPHIN PEPTIDES DECREASE THE PROLIFERATION OF PROSTATIC-CANCER CELL-LINES (LNCAP, PC3 AND DU145) THROUGH A PARTIAL INTERACTION WITH OPIOID RECEPTORS

Opioid agonists (ethylketocyclazocine, etolphine, [D-Ala(2),D-Leu(5)]e nkephalin (DADLE), [D-Ala(2), N-Me-Phe(4)-Gly-ol]enkephalin (DAGO), [D -Ser(2),Leu(5)]enkepharin-Thr(6) (DSLET) and morphine were found to in hibit the proliferation of human prostate cancer cell lines (LNCaP, DU 145, and PC3), in a dose-dependent manner. The 50% inhibitory concentr ations (IC50) were in the picomolar range. In many cases, this effect was antagonized by the general opioid antagonist, diprenorphine, indic ating the existence of specific opioid binding sites. Saturation bindi ng experiments with selective ligands and effecters showed no opioid s ites on the LNCaP cell line, kappa(1) and mu sites on the PC3 cell lin e, and kappa(1), kappa(3) and mu sites on the DU145 cell line. In othe r cases, the opioid effect was not antagonized by diprenorphine, indic ating that the action of opioids might be mediated through other membr ane receptors. Furthermore, casomorphin peptides, issued from bovine a lpha-(alpha-casein-90-95 and alpha-casein-90-96) and beta-caseins (bet a-casomorphin and beta-casomorphin-1-5), and human alpha(S1)-casein (a lpha(S1)-casomorphin and alpha(S1)-casomorphin amide) inhibited cell p roliferation of human prostate cell lines, also by a mechanism partly involving opioid receptors. As opioid neurons can be found in the pros tate gland, and casomorphin peptides might reach the gland through the general circulation, the above findings indicate a putative role of o pioids in prostate cancer cell growth. (C) 1997 Elsevier Science B.V.