The opioid agonist ethylketocyclazocine reverts the rapid, non-genomic effects of membrane testosterone receptors in the human prostate LNCaP cell line

• Published in: Experimental cell research 2004-04, Vol.294 (2), p.434-445
• Main Authors: Kampa, Marilena, Papakonstanti, Evangelia A, Alexaki, Vassilia-Ismini, Hatzoglou, Anastassia, Stournaras, Christos, Castanas, Elias
• Format: Article
• Language: English
• Subjects: Actin Cytoskeleton - drug effects; Actin Cytoskeleton - metabolism; Analgesics, Opioid - pharmacology; Androgen receptor (membrane); Binding Sites - drug effects; Binding Sites - physiology; Binding, Competitive - drug effects; Binding, Competitive - physiology; Carcinoma - drug therapy; Carcinoma - metabolism; Cell Division - drug effects; Cell Division - physiology; Cell Membrane - drug effects; Cell Membrane - metabolism; Ethylketocyclazocine - pharmacology; Focal Adhesion Kinase 1; Focal Adhesion Protein-Tyrosine Kinases; Humans; Male; Opioid Peptides - agonists; Opioid Peptides - metabolism; Opioids; Prostate cancer cell (LNCaP); Prostate-Specific Antigen - metabolism; Prostate-Specific Antigen - secretion; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - metabolism; Protein-Tyrosine Kinases - drug effects; Protein-Tyrosine Kinases - metabolism; Reaction Time - drug effects; Reaction Time - physiology; Receptors, Androgen - drug effects; Receptors, Androgen - metabolism; Serum Albumin, Bovine - pharmacology; Signal Transduction - drug effects; Signal Transduction - physiology; Testosterone - analogs & derivatives; Testosterone - metabolism; Testosterone - pharmacology; Tumor Cells, Cultured
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2003.11.027

Neuropeptides influence cancer cell replication and growth. Opioid peptides, and opiergic neurons are found in the prostate gland, and they are proposed to exert a role in tumor regulation, influencing cancer cell growth, as opioid agonists inhibit cell growth in several systems, including the human prostate cancer cell line LNCaP. In the same cell line, the existence of membrane testosterone receptors was recently reported, which increase, in a non-genomic manner, the secretion of PSA, and modify actin cytoskeleton dynamics, through the signaling cascade FAK→PI-3 kinase→Cdc42/Rac1. In the present work, we present data supporting that the general opioid agonist Ethylketocyclazocine (EKC) decreases testosterone-BSA (a non-internalizable testosterone analog) induced PSA secretion. Furthermore, we report that this opioid affects this non-genomic testosterone action, by modifying the distribution of the actin cytoskeleton in the cells, disrupting the above signaling cascade. In addition, after long (>24 h) incubation, opioids decrease the number of membrane testosterone receptors, and reverse their effect on the signaling molecules. In conclusion, our results provide some new insights of a possible action of opioids in prostate cancer control by interfering with the action and the expression of membrane testosterone receptors and signaling.