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Pristimerin induces apoptosis by targeting the proteasome in prostate cancer cells
文献类型：期刊论文
| 作者 | Li, Lihua1,3; Yang, Huanjie1,3; Landis-Piwowar, Kristin R.1,3; Lu, Dayan4; Yuan, Ping4; Reddy, G. Prem-Veer1,2,3; Yuan, Xiao4; Dou, Q. Ping1,3 |
| 刊名 | JOURNAL OF CELLULAR BIOCHEMISTRY
 |
| 出版日期 | 2008 |
| 卷号 | 103期号:1页码:234-244 |
| 关键词 | pristimerin proteasome inhibition natural compounds apoptosis prostate cancer |
| ISSN号 | 0730-2312 |
| DOI | 10.1002/jcb.21399 |
| 英文摘要 | Pristimerin is a natural product derived from the Celastraceae and Hippocrateaceae families that were used as folk medicines for anti inflammation in ancient times. Although it has been shown that pristimerin induces apoptosis in breast cancer cells, the involved mechanism of action is unknown. The purpose of the current study is to investigate the primary target of pristimerin in human cancer cells, using prostate cancer cells as a working model. Nucleophilic susceptibility and in silico docking studies show that C-6 of pristimerin is highly susceptible towards a nucleophilic attack by the hydroxyl group of N-terminal threonine of the proteasomal chymotrypsin subunit. Consistently, pristimerin potently inhibits the chymotrypsin-like activity of a purified rabbit 20S proteasome (IC50 2.2 mu mol/L) and human prostate cancer 26S proteasome (IC50 3.0 mu mol/L). The accumulation of ubiquitinated proteins and three proteasome target proteins, Bax, p27 and I kappa B-alpha., in androgen receptor (AR)-negative PC-3 prostate cancer cells supports the conclusion that proteasome inhibition by pristimerin is physiologically functional. This observed proteasome inhibition subsequently led to the induction of apoptotic cell death in a dose- and kinetic-dependent manner. Furthermore, in AR-positive, androgen-dependent LNCaP and AR-positive, androgen-independent C4-2B prostate cancer cells, proteasome inhibition by pristimerin results in suppression of AR protein prior to apoptosis. Our data demonstrate, for the first time, that the proteasome is a primary target of pristimerin in prostate cancer cells and inhibition of the proteasomal chymotrypsin-like activity by pristimerin is responsible for its cancer cell death-inducing property. |
| WOS研究方向 | Biochemistry & Molecular Biology ; Cell Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000252334400019 |
| 出版者 | WILEY-LISS |
| 源URL | [http://202.127.146.157/handle/2RYDP1HH/1120]  |
| 专题 | 中国科学院武汉植物园 |
| 通讯作者 | Dou, Q. Ping |
| 作者单位 | 1.Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA 2.Henry Ford Hosp, Vattikuti Urol Inst, Detroit, MI USA 3.Wayne State Univ, Sch Med, Prevent Program, Barbara Ann Karmanos Canc Inst, Detroit, MI 48201 USA 4.Chinese Acad Sci, Wuhan Bot Garden, New Drug Res Labs, Wuhan 430074, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Lihua,Yang, Huanjie,Landis-Piwowar, Kristin R.,et al. Pristimerin induces apoptosis by targeting the proteasome in prostate cancer cells[J]. JOURNAL OF CELLULAR BIOCHEMISTRY,2008,103(1):234-244. |
| APA | Li, Lihua.,Yang, Huanjie.,Landis-Piwowar, Kristin R..,Lu, Dayan.,Yuan, Ping.,...&Dou, Q. Ping.(2008).Pristimerin induces apoptosis by targeting the proteasome in prostate cancer cells.JOURNAL OF CELLULAR BIOCHEMISTRY,103(1),234-244. |
| MLA | Li, Lihua,et al."Pristimerin induces apoptosis by targeting the proteasome in prostate cancer cells".JOURNAL OF CELLULAR BIOCHEMISTRY 103.1(2008):234-244. |
入库方式： OAI收割
来源：武汉植物园
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