| Oleanolic acid arrests cell cycle and induces apoptosis via ROS-mediated mitochondrial depolarization and lysosomal membrane permeabilization in human pancreatic cancer cells | |
Wei, Jianteng1,3; Liu, Ming1; Liu, Haizhou1; Wang, Hui1,3 ; Wang, Fengxia4; Zhang, Yuyan5; Han, Lijun1; Lin, Xiukun1,2; Lin, XK
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| 2013-08-01 | |
| 发表期刊 | JOURNAL OF APPLIED TOXICOLOGY
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| ISSN | 0260-437X |
| 卷号 | 33期号:8页码:756-765 |
| 文章类型 | Article |
| 摘要 | Oleanolic acid (OA), a pentacyclic triterpenoid, exhibits potential anti-tumor activity against many tumor cell lines. This study aims to examine the anti-tumor activity of OA on pancreatic cancer cells and its potential molecular mechanism. The results showed that the proliferation of Panc-28 cells was inhibited by OA in a concentration-dependent manner, with an IC50 (The half maximal inhibitory concentration) value of 46.35 mu g ml-1, as determined by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The cell cycle was arrested in S phase and G2/M phase by OA. The study also showed that OA could induce remarkable apoptosis, evidenced by an increased percentage of early/late apoptotic cells, DNA ladder and nuclear morphology change. Further study revealed that OA could induce Reactive Oxygen Species (ROS) generation, mitochondrial depolarization, release of cytochrome C, lysosomal membrane permeabilization and leakage of cathepin B. The expression of apoptosis-correlated proteins was also affected in cells treated with OA, including activation of caspases-3/9 and cleavage of PARP. Further study confirmed that ROS scavenger vitamin C could reverse the apoptosis induced by OA in Panc-28 cells. Our results provide evidence that OA arrests the cell cycle and induces apoptosis, possibly via ROS-mediated mitochondrial and a lysosomal pathway in Panc-28 cells. Copyright (c) 2012 John Wiley & Sons, Ltd.; Oleanolic acid (OA), a pentacyclic triterpenoid, exhibits potential anti-tumor activity against many tumor cell lines. This study aims to examine the anti-tumor activity of OA on pancreatic cancer cells and its potential molecular mechanism. The results showed that the proliferation of Panc-28 cells was inhibited by OA in a concentration-dependent manner, with an IC50 (The half maximal inhibitory concentration) value of 46.35 mu g ml-1, as determined by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The cell cycle was arrested in S phase and G2/M phase by OA. The study also showed that OA could induce remarkable apoptosis, evidenced by an increased percentage of early/late apoptotic cells, DNA ladder and nuclear morphology change. Further study revealed that OA could induce Reactive Oxygen Species (ROS) generation, mitochondrial depolarization, release of cytochrome C, lysosomal membrane permeabilization and leakage of cathepin B. The expression of apoptosis-correlated proteins was also affected in cells treated with OA, including activation of caspases-3/9 and cleavage of PARP. Further study confirmed that ROS scavenger vitamin C could reverse the apoptosis induced by OA in Panc-28 cells. Our results provide evidence that OA arrests the cell cycle and induces apoptosis, possibly via ROS-mediated mitochondrial and a lysosomal pathway in Panc-28 cells. Copyright (c) 2012 John Wiley & Sons, Ltd. |
| 关键词 | Oleanolic Acid Apoptosis Ros Mitochondrial Depolarization Lysosomal Membrane Permeabilization |
| 学科领域 | Toxicology |
| DOI | 10.1002/jat.2725 |
| URL | 查看原文 |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS研究方向 | Toxicology |
| WOS类目 | Toxicology |
| WOS记录号 | WOS:000320778400006 |
| WOS关键词 | URSOLIC ACID ; CYTOCHROME-C ; DNA-DAMAGE ; ACTIVATION ; EXPRESSION ; STATISTICS ; INDUCTION ; CLEAVAGE ; GROWTH ; BCL-2 |
| WOS标题词 | Science & Technology ; Life Sciences & Biomedicine |
| 引用统计 | |
| 文献类型 | 期刊论文 |
| 条目标识符 | http://ir.qdio.ac.cn/handle/337002/16709 |
| 专题 | 海洋生物技术研发中心 实验海洋生物学重点实验室 |
| 通讯作者 | Lin, XK |
| 作者单位 | 1.Chinese Acad Sci, Inst Oceanol, Qingdao 266071, Peoples R China 2.Capital Med Univ, Dept Pharmacol, Beijing 100069, Peoples R China 3.Chinese Acad Sci, Grad Univ, Beijing 100049, Peoples R China 4.Shandong Univ, Sch Pharm, Jinan 250100, Shandong, Peoples R China 5.Qingdao Univ Sci & Technol, Coll Chem Engn, Qingdao 266042, Peoples R China |
| 第一作者单位 | 中国科学院海洋研究所 |
| 推荐引用方式 GB/T 7714 | Wei, Jianteng,Liu, Ming,Liu, Haizhou,et al. Oleanolic acid arrests cell cycle and induces apoptosis via ROS-mediated mitochondrial depolarization and lysosomal membrane permeabilization in human pancreatic cancer cells[J]. JOURNAL OF APPLIED TOXICOLOGY,2013,33(8):756-765. |
| APA | Wei, Jianteng.,Liu, Ming.,Liu, Haizhou.,Wang, Hui.,Wang, Fengxia.,...&Lin, XK.(2013).Oleanolic acid arrests cell cycle and induces apoptosis via ROS-mediated mitochondrial depolarization and lysosomal membrane permeabilization in human pancreatic cancer cells.JOURNAL OF APPLIED TOXICOLOGY,33(8),756-765. |
| MLA | Wei, Jianteng,et al."Oleanolic acid arrests cell cycle and induces apoptosis via ROS-mediated mitochondrial depolarization and lysosomal membrane permeabilization in human pancreatic cancer cells".JOURNAL OF APPLIED TOXICOLOGY 33.8(2013):756-765. |
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