Inhibition on Proteasome β1 Subunit Might Contribute to the Anti-Cancer Effects of Fangchinoline in Human Prostate Cancer Cells
| العنوان: | Inhibition on Proteasome β1 Subunit Might Contribute to the Anti-Cancer Effects of Fangchinoline in Human Prostate Cancer Cells |
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| المؤلفون: | Yu Lu, Miao Liu, Peng Sun, Xiao-Bo Qu, Lihong Hu, Baohong Jiang, Wanying Wu, Dong Li, Li-Xing Feng, Dean Guo, Min Yang, Xuan Liu |
| المصدر: | PLoS ONE, Vol 10, Iss 10, p e0141681 (2015) PLoS ONE |
| بيانات النشر: | Public Library of Science (PLoS), 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Male, Proteasome Endopeptidase Complex, Gene Expression, lcsh:Medicine, Apoptosis, Benzylisoquinolines, chemistry.chemical_compound, Mice, Bcl-2-associated X protein, Ubiquitin, Catalytic Domain, Cell Line, Tumor, LNCaP, Animals, Humans, lcsh:Science, Cell Proliferation, bcl-2-Associated X Protein, Multidisciplinary, biology, Cell growth, lcsh:R, Ubiquitination, Prostatic Neoplasms, Transfection, Cell Cycle Checkpoints, Antineoplastic Agents, Phytogenic, Xenograft Model Antitumor Assays, Recombinant Proteins, Cell biology, Tetrandrine, Enzyme Activation, Disease Models, Animal, Protein Subunits, Proteasome, chemistry, Gene Knockdown Techniques, Cancer cell, biology.protein, I-kappa B Proteins, lcsh:Q, Proteasome Inhibitors, Cyclin-Dependent Kinase Inhibitor p27, Protein Binding, Research Article |
| الوصف: | Fangchinoline is a bisbenzylisoquinoline alkaloid isolated from Radix Stephaniae tetrandrae S. Moore. Fangchinoline and its structure analogue, tetrandrine, exhibited direct binding affinity with recombinant human proteasome β1 subunit and also inhibited its activity in vitro. In cultured prostate PC-3 cells and LnCap cells, fangchinoline could dose-dependently inhibit cell proliferation and caspase-like activity of cellular proteasome which was mediated by proteasome β1 subunit. The inhibitive effect of fangchinoline on caspase-like activity of proteasome was also observed in purified human erythrocyte 20S proteasome. In PC-3 cells, fangchinoline induced cell cycle arrest at G0/G1 phase and apoptosis. Treatment of PC-3 tumor-bearing nude mice with fangchinoline inhibited tumor growth, induced apoptosis and also caused decrease in proteasome activities in tumor xenografts. Dose-dependent and time-dependent accumulation of ubiquitinated proteins and important proteasome substrates such as p27, Bax and IκB-α were observed in fangchinoline-treated cells. Over-expression of proteasome β1 subunit by plasmid transfection increased sensitivity of cells to the cytotoxicity of fangchinoline while knockdown of proteasome β1 subunit ameliorated cytotoxicity of fangchinoline in PC-3 cells. Results of the present study suggested that proteasome inhibition was involved in the anti-cancer effects of fangchinoline. Fangchinoline and its structure analogues might be new natural proteasome inhibitors targeting β1 subunit. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::07b7b467df3bd9603a84fbbfd81ca86cTest http://europepmc.org/articles/PMC4626104?pdf=renderTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....07b7b467df3bd9603a84fbbfd81ca86c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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