Pseudolaric acid B induces apoptosis via proteasome-mediated Bcl-2 degradation in hormone-refractory prostate cancer DU145 cells
Zhao, Dandan1,2; Lin, Feng1; Wu, Xingde3; Zhao, Qinshi3; Zhao, Binjiahui1; Lin, Ping1; Zhang, Yanlong2; Yu, Xiaoguang1
2012-06-01
发表期刊TOXICOLOGY IN VITRO
ISSN0887-2333
卷号26期号:4页码:595-602
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.
关键词Pseudolaric Acid b Hormone-refractory Prostate Cancer Apoptosis Bcl-2 Degradation Proteasome Reactive Oxygen Species
资助信息Natural Science Foundation of Heilongjiang Province, China[QC2011C118]; International Scientific and Technological Cooperation Project of Heilongjiang Province, China[WB08B08]; Graduate Innovation Foundation of Harbin Medical University, China[HCXB2010003]
学科领域Toxicology
DOI10.1016/j.tiv.2012.02.004
收录类别SCI
语种英语
WOS研究方向Toxicology
WOS类目Toxicology
WOS记录号WOS:000303702900007
引用统计
被引频次:22[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.kib.ac.cn/handle/151853/10455
专题植物化学与西部植物资源持续利用国家重点实验室
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
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Zhao, Dandan,Lin, Feng,Wu, Xingde,et al. Pseudolaric acid B induces apoptosis via proteasome-mediated Bcl-2 degradation in hormone-refractory prostate cancer DU145 cells[J]. TOXICOLOGY IN VITRO,2012,26(4):595-602.
APA Zhao, Dandan.,Lin, Feng.,Wu, Xingde.,Zhao, Qinshi.,Zhao, Binjiahui.,...&Yu, Xiaoguang.(2012).Pseudolaric acid B induces apoptosis via proteasome-mediated Bcl-2 degradation in hormone-refractory prostate cancer DU145 cells.TOXICOLOGY IN VITRO,26(4),595-602.
MLA Zhao, Dandan,et al."Pseudolaric acid B induces apoptosis via proteasome-mediated Bcl-2 degradation in hormone-refractory prostate cancer DU145 cells".TOXICOLOGY IN VITRO 26.4(2012):595-602.
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