Somatostatin effects on the proteome of the LNCaP cell-line.
Some clinical results indicate that somatostatin (sms) might be useful in the treatment of advanced prostate cancer (HRPC). Because of its transient in vivo half-life only more stable derivatives of sms are of interest in this context. Recent studies have shown that natural sms can be conjugated to a carbohydrate (smsdx) with preservation of sms-like effects on the prostatic tumor cell proteome. The present study identifies some of the affected proteins in an effort to elucidate pathways and proteins that might be of importance for the potential usefulness of sms treatment in HRPC. After incubating the LNCaP cell-line with sms14/smsdx, comparative proteomics was used for analysing and identifying affected proteins. Protein expression patterns were analysed with two-dimensional polyacrylamide gel electrophoresis and mass spectrometry. Catalytic mitochondrial and mitochondrial-associated proteins were significantly affected (fold change approximately 2 or higher) and they were in general up-regulated. Apoptosis-related proteins were both up-regulated (VDAC1, VDAC2) and down-regulated (PRDX2, TCTP). The fold change was >2 for PRDX2 and <2 for the others. There was a strong agreement between sms and smsdx on the up- and down-regulation of proteins. Sms/smsdx triggered up-regulation of catalytic mitochondrial proteins and seemed to affect apoptosis-related proteins. This could indicate important pathways on which smsdx might be able to curb the progression of HRPC. The results encourage a pending clinical phase II study.
Liu
Zhaoxu
Z
Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden.
Bengtsson
Sofia
S
Krogh
Morten
M
Marquez
Marcela
M
Nilsson
Sten
S
James
Peter
P
Aliaya
Ayodele
A
Holmberg
Anders R
AR
D002384:Catalysis; D045744:Cell Line, Tumor; D018450:Disease Progression; D015180:Electrophoresis, Gel, Two-Dimensional; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D009363:Neoplasm Proteins / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D020543:Proteome; D040901:Proteomics / Q000379:methods*; D013004:Somatostatin / Q000494:pharmacology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D000090324:Tumor Protein, Translationally-Controlled 1
D009363:Neoplasm Proteins; D020543:Proteome; C000715647:TPT1 protein, human; D000090324:Tumor Protein, Translationally-Controlled 1; D013004:Somatostatin