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题名: Pseudolaric acid B induces apoptosis via proteasome-mediated Bcl-2 degradation in hormone-refractory prostate cancer DU145 cells
作者: Zhao, Dandan1, 2; Lin, Feng1; Wu, Xingde3; null(赵勤实)3; Zhao, Binjiahui1; Lin, Ping1; Zhang, Yanlong2; Yu, Xiaoguang1
刊名: TOXICOLOGY IN VITRO
关键词: Pseudolaric acid B ; Hormone-refractory prostate cancer ; Apoptosis ; Bcl-2 degradation ; Proteasome ; Reactive oxygen species
英文摘要: Pseudolaric acid B (PAB), a natural diterpene acid present in the traditional Chinese medicinal herb Tu-Jin-Pi, exerted anticancer effects on various cancer cells. However, the effect of PAB on DU145 cells, an in vitro model of hormone-refractory prostate cancer (HRPC), has not been reported previously. In the study. PAB significantly suppressed proliferation of DU145 cells in a dose-dependent manner without obvious cytotoxicity. IC50 values of 0.89 +/- 0.18 and 0.76 +/- 0.151 mu M at 48 h was determined by Cell counting kit (CCK-8) assay and clone formation assay, respectively. PAB also induced DU145 cells apoptosis as confirmed by typical morphological changes and Annexin V-FITC staining. Furthermore, we demonstrated that PAB caused a concentration-dependent elevation of reactive oxygen species (ROS) level in DU145 cells, and N-acetyl-L-cysteine (NAC, a well-known ROS scavenger) could block PAB-induced ROS generation and apoptosis. Western blotting and/or caspase activity data indicated that PAB downregulated anti-apoptotic Bcl-2 protein and activated caspase-9 and caspase-3, which were largely rescued by NAC or MG-132 (proteasome inhibitor). Taken together, these findings provide the first evidence that PAB may inhibit growth of HRPC DU145 cells and induce apoptosis through ROS generation and Bcl-2 degradation via the activation of the ubiquitin-proteasome pathway. (C) 2012 Elsevier Ltd. All rights reserved.
出版日期: 2012-06-01
卷号: 26, 期号:4, 页码:595-602
DOI标识: 10.1016/j.tiv.2012.02.004
语种: 英语
ISSN号: 0887-2333
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内容类型: 期刊论文
URI标识: http://ir.kib.ac.cn/handle/151853/10455
Appears in Collections:植物化学与西部植物资源持续利用国家重点实验室_期刊论文

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作者单位: 1.Harbin Med Univ, Coll Basic Med Sci, Dept Biochem & Mol Biol, Harbin 150081, Peoples R China
2.Heilongjiang Univ, Coll Life Sci, Prov Key Lab Mol Biol, Harbin 150086, Peoples R China
3.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources W China, Heilongtan 650204, Kunming, Peoples R China

Recommended Citation:
Zhao, DD; Lin, F; Wu, XD; Zhao, QS; Zhao, BJH; Lin, P; Zhang, YL; Yu, XG.Pseudolaric acid B induces apoptosis via proteasome-mediated Bcl-2 degradation in hormone-refractory prostate cancer DU145 cells,TOXICOLOGY IN VITRO,2012,26(4):595-602
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