1. Identification of simvastatin-regulated targets associated with JNK activation in DU145 human prostate cancer cell death signaling
- Author
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Eun Joo Jung, Ky Hyun Chung, and Choong Won Kim
- Subjects
0301 basic medicine ,Programmed cell death ,Proteomic analysis ,Vimentin ,Docetaxel ,urologic and male genital diseases ,Biochemistry ,03 medical and health sciences ,DU145 cell death ,0302 clinical medicine ,Downregulation and upregulation ,DU145 ,polycyclic compounds ,Heterogeneous-Nuclear Ribonucleoprotein K ,Molecular Biology ,biology ,Chemistry ,Kinase ,Simvastatin-regulated targets ,General Medicine ,Articles ,030104 developmental biology ,JNK ,030220 oncology & carcinogenesis ,Cancer cell ,Cancer research ,biology.protein ,Thioredoxin - Abstract
The results of this study show that c-Jun N-terminal kinase (JNK) activation was associated with the enhancement of docetaxel-induced cytotoxicity by simvastatin in DU145 human prostate cancer cells. To better understand the basic molecular mechanisms, we investigated simvastatin-regulated targets during simvastatin-induced cell death in DU145 cells using two-dimensional (2D) proteomic analysis. Thus, vimentin, Ras-related protein Rab-1B (RAB1B), cytoplasmic hydroxymethylglutaryl-CoA synthase (cHMGCS), thioredoxin domain-containing protein 5 (TXNDC5), heterogeneous nuclear ribonucleoprotein K (hnRNP K), N-myc downstream-regulated gene 1 (NDRG1), and isopentenyl-diphosphate Delta-isomerase 1 (IDI1) protein spots were identified as simvastatin-regulated targets involved in DU145 cell death signaling pathways. Moreover, the JNK inhibitor SP600125 significantly inhibited the upregulation of NDRG1 and IDI protein levels by combination treatment of docetaxel and simvastatin. These results suggest that NDRG1 and IDI could at least play an important role in DU145 cell death signaling as simvastatinregulated targets associated with JNK activation. [BMB Reports 2017; 50(9): 466-471].
- Published
- 2017