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 alkaloids and casomorphin peptides decrease the proliferation of prostatic cancer cell lines (LNCaP, PC3 and DU145) through a partial interaction with opioid receptors
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DOI：
10.1016/s0014-2999(97)01213-2
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发表时间：
1997-09-24
影响因子：
5
通讯作者：
Castanas, E
中科院分区：
文献类型：
--
作者：
Kampa, M;Bakogeorgou, E;Castanas, E
阿片激动剂（乙基酮环唑辛、依托啡、[D-Ala（2），D-Leu（5）]脑啡肽（DADLE）、[D-Ala（2），N-Me-Phe（4）-Gly-ol]脑啡肽（DAGO）、[D-Ser（2），Leu（5）]脑啡肽-Thr（6）（DSLET）和吗啡以剂量依赖性方式抑制人前列腺癌细胞系（LNCaP、DU 145和PC 3）的增殖。50%抑制浓度（IC 50）在皮摩尔范围内。在许多情况下，这种作用被一般阿片类拮抗剂二丙诺啡拮抗，表明存在特异性阿片类结合位点。用选择性配体和效应物进行的饱和结合实验显示，LNCaP细胞系上没有阿片样物质位点，PC 3细胞系上没有kappa（1）和mu位点，DU 145细胞系上没有kappa（1）、kappa（3）和mu位点。在其他情况下，阿片样物质的作用不被二丙诺啡拮抗，表明阿片样物质的作用可能是通过其他膜受体介导的。此外，由牛α-（α-酪蛋白-90-95和α-酪蛋白-90-96）和β-酪蛋白（β-酪啡肽和β-酪啡肽-1-5）以及人α（S1）-酪蛋白（α（S1）-酪啡肽和α（S1）-酪啡肽酰胺）产生的酪啡肽也通过部分涉及阿片受体的机制抑制人前列腺细胞系的细胞增殖。由于阿片样物质神经元可以在前列腺中发现，并且酪啡肽可能通过全身循环到达腺体，因此上述发现表明阿片样物质在前列腺癌细胞生长中的假定作用。(C)1997年Elsevier Science B.V.
Opioid agonists (ethylketocyclazocine, etolphine, [D-Ala(2),D-Leu(5)]enkephalin (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 inhibit the proliferation of human prostate cancer cell lines (LNCaP, DU145, and PC3), in a dose-dependent manner. The 50% inhibitory concentrations (IC50) were in the picomolar range. In many cases, this effect was antagonized by the general opioid antagonist, diprenorphine, indicating the existence of specific opioid binding sites. Saturation binding experiments with selective ligands and effecters showed no opioid sites on the LNCaP cell line, kappa(1) and mu sites on the PC3 cell line, and kappa(1), kappa(3) and mu sites on the DU145 cell line. In other cases, the opioid effect was not antagonized by diprenorphine, indicating that the action of opioids might be mediated through other membrane receptors. Furthermore, casomorphin peptides, issued from bovine alpha-(alpha-casein-90-95 and alpha-casein-90-96) and beta-caseins (beta-casomorphin and beta-casomorphin-1-5), and human alpha(S1)-casein (alpha(S1)-casomorphin and alpha(S1)-casomorphin amide) inhibited cell proliferation of human prostate cell lines, also by a mechanism partly involving opioid receptors. As opioid neurons can be found in the prostate gland, and casomorphin peptides might reach the gland through the general circulation, the above findings indicate a putative role of opioids in prostate cancer cell growth. (C) 1997 Elsevier Science B.V.