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Inhibition on Proteasome beta 1 Subunit Might Contribute to the Anti-Cancer Effects of Fangchinoline in Human Prostate Cancer Cells

文献类型：期刊论文

作者Li, Dong1,2; Lu, Yu3; Sun, Peng2; Feng, Li-Xing2; Liu, Miao2; Hu, Li-Hong2; Wu, Wan-Ying2; Jiang, Bao-Hong2; Yang, Min2; Qu, Xiao-Bo1
刊名PLOS ONE
出版日期2015-10-29
卷号10期号:10
ISSN号1932-6203
DOI10.1371/journal.pone.0141681
文献子类Article
英文摘要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 beta 1 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 beta 1 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 nudemice 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 I kappa B-a were observed in fangchinoline-treated cells. Over-expression of proteasome beta 1 subunit by plasmid transfection increased sensitivity of cells to the cytotoxicity of fangchinoline while knockdown of proteasome beta 1 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 beta 1 subunit.
WOS关键词KAPPA-B-ALPHA ; RADIX-STEPHANIAE-TETRANDRAE ; CYCLE ARREST ; CARCINOMA-CELLS ; MOLECULAR TARGETS ; LEUKEMIA-CELLS ; G(1) ARREST ; IN-VIVO ; APOPTOSIS ; EXPRESSION
资助项目Shanghai Science & Technology Support Program[13431900401] ; National Nature Science Foundation of China[81373964] ; Shanghai Science & Technology Innovation Action Program[15140904800] ; National Science & Technology Major Project of China[2014ZX09301-306-03] ; Twelfth Five-Year National Science & Technology Support Program[2012BAI29B06] ; Nanjing Tianyi Bioscience Co. Ltd[00000000]
WOS研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:000363920300068
出版者PUBLIC LIBRARY SCIENCE
源URL[http://119.78.100.183/handle/2S10ELR8/276351]  
专题上海中药现代化研究中心
通讯作者Guo, De-An
作者单位1.Changchun Univ Chinese Med, Changchun 130117, Peoples R China;
2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China;
3.Nanjing Tianyi Biosci Co Ltd, Nanjing 210061, Jiangsu, Peoples R China
推荐引用方式
GB/T 7714		 Li, Dong,Lu, Yu,Sun, Peng,et al. Inhibition on Proteasome beta 1 Subunit Might Contribute to the Anti-Cancer Effects of Fangchinoline in Human Prostate Cancer Cells[J]. PLOS ONE,2015,10(10).
APA Li, Dong.,Lu, Yu.,Sun, Peng.,Feng, Li-Xing.,Liu, Miao.,...&Liu, Xuan.(2015).Inhibition on Proteasome beta 1 Subunit Might Contribute to the Anti-Cancer Effects of Fangchinoline in Human Prostate Cancer Cells.PLOS ONE,10(10).
MLA Li, Dong,et al."Inhibition on Proteasome beta 1 Subunit Might Contribute to the Anti-Cancer Effects of Fangchinoline in Human Prostate Cancer Cells".PLOS ONE 10.10(2015).

入库方式： OAI收割

来源：上海药物研究所

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