The mechanisms underlying prostate cancer progression are poorly understood. Proteins responsive to androgens may be involved in the development and progression of prostate cancer and the ultimate failure of androgen-ablation therapy. Therapy with somatostatin (sms) analogues could be a possible therapeutic alternative to chemotherapy in hormone refractory prostate cancer patients. We used two prostate cancer cell-lines, LNCaP (androgen-dependent) and DU145 (androgen-independent), to compare the protein expressions. Both cell lines were treated with sms and its derivative smsdx. Smsdx is a glycosylated poly sms with high stability suitable for clinical use. A comparison study of protein expression was analyzed by means of two-dimensional gel electrophoresis (2DE) followed by mass spectrometric analysis. Marked quantitative differences were observed in the protein expression profiles in sms/smsdx treated LNCaP and DU145 cells compared to the control cells. One third of the detected proteins were differentially expressed (PRDXs, hnRNPs, HSPs, RKIP). Concordance in protein expression patterns was observed between smsdx and sms treated cells with strong agreement between the up- and down-regulation of proteins. Fifty-eight (isoforms of 49 proteins) protein spots were identified and found differentially expressed at 2-fold change between LNCaP and DU145 cells. Thirty-one proteins in LNCaP have higher expressions than in DU145. Twenty-seven proteins in DU145 have higher expressions than in LNCaP. Most of the differentially expressed proteins (2-fold) between LNCaP and DU145 cells were affected by sms/smsdx treatment (1.2- to 2.6-fold change). Sms/smsdx affects the mitochondria of prostate cancer cells in a way that eventually triggers mitochondrial-mediated apoptosis. Regulation of certain proteins (e.g., RKIP, VDACs) by sms/smsdx suggests that sms/smsdx exerts its effects on prostate cancer cells via MAPK pathway and by regulating the activities of phosphotyrosine phosphatases.

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