| p38 MAPK Signaling Mediates Mitochondrial Apoptosis in Cancer Cells Induced by Oleanolic Acid | |
| Liu, Jia1; Wu, Ning1; Ma, Lei-Na3; Zhong, Jia-Teng6; Liu, Ge1,4; Zheng, Lan-Hong2; Lin, Xiu-Kun1,5; Zheng, LH (reprint author), Chinese Acad Fishery Sci, Yellow Sea Fisheries Res Inst, Qingdao, Peoples R China. | |
| 2014 | |
| 发表期刊 | ASIAN PACIFIC JOURNAL OF CANCER PREVENTION
 |
| 卷号 | 15期号:11页码:4519-4525 |
| 文章类型 | Article |
| 摘要 | Oleanolic acid (OA) is a nutritional component widely distributed in various vegetables. Although it has been well recognized for decades that OA exerts certain anti-tumor activity by inducing mitochondria-dependent apoptosis, it is still unclear that what molecular signaling is responsible for this effect. In this study, we employed cancer cell lines, A549, BXPC-3, PANC-1 and U2OS to elucidate the molecular mechanisms underlying OA antitumor activity. We found that activation of MAPK pathways, including p-38 MAPK, JNK and ERK, was triggered by OA in both a dose and time-dependent fashion in all the tested cancer cells. Activation was accompanied by cleavage of caspases and PARP as well as cytochrome C release. SB203580 (p38 MAPK inhibitor), but not SP600125 (JNK inhibitor) and U0126 (ERK inhibitor), rescued the pro-apoptotic effect of OA on A549 and BXPC-3 cells. OA induced p38 MAPK activation promoted mitochondrial translocation of Bax and Bim, and inhibited Bcl-2 function by enhancing their phosphorylation. OA can induce reactive oxygen species (ROS)-dependent ASK1 activation, and this event was indispensable for p38 MAPK-dependent apoptosis in cancer cells. In vivo, p38 MAPK knockdown A549 tumors proved resistant to the growth-inhibitory effect of OA. Collectively, we elucidated that activation of ROS/ASK1/p38 MAPK pathways is responsible for the apoptosis stimulated by OA in cancer cells. Our finding can contribute to a better understanding of molecular mechanisms underlying the antitumor activity of nutritional components. |
| 关键词 | Oleanolic Acid Apoptosis P38 Mapk Cancer Ros |
| 学科领域 | Oncology |
| DOI | 10.7314/APJCP.2014.15.11.4519 |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000338634900023 |
| 引用统计 | |
| 文献类型 | 期刊论文 |
| 条目标识符 | http://ir.qdio.ac.cn/handle/337002/24235 |
| 专题 | 海洋生物技术研发中心 |
| 通讯作者 | Zheng, LH (reprint author), Chinese Acad Fishery Sci, Yellow Sea Fisheries Res Inst, Qingdao, Peoples R China. |
| 作者单位 | 1.Chinese Acad Sci, Inst Oceanol, Qingdao, Peoples R China 2.Chinese Acad Fishery Sci, Yellow Sea Fisheries Res Inst, Qingdao, Peoples R China 3.Ocean Univ China, Sch Med & Pharm, Dept Mol Biol, Qingdao, Peoples R China 4.Univ Chinese Acad Sci, Grad Sch, Beijing, Peoples R China 5.Capital Med Univ, Dept Pharmacol, Beijing, Peoples R China 6.Jilin Univ, Norman Bethune Coll Med, Dept Pathophysiol, Changchun 130023, 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 | Liu, Jia,Wu, Ning,Ma, Lei-Na,et al. p38 MAPK Signaling Mediates Mitochondrial Apoptosis in Cancer Cells Induced by Oleanolic Acid[J]. ASIAN PACIFIC JOURNAL OF CANCER PREVENTION,2014,15(11):4519-4525. |
| APA | Liu, Jia.,Wu, Ning.,Ma, Lei-Na.,Zhong, Jia-Teng.,Liu, Ge.,...&Zheng, LH .(2014).p38 MAPK Signaling Mediates Mitochondrial Apoptosis in Cancer Cells Induced by Oleanolic Acid.ASIAN PACIFIC JOURNAL OF CANCER PREVENTION,15(11),4519-4525. |
| MLA | Liu, Jia,et al."p38 MAPK Signaling Mediates Mitochondrial Apoptosis in Cancer Cells Induced by Oleanolic Acid".ASIAN PACIFIC JOURNAL OF CANCER PREVENTION 15.11(2014):4519-4525. |
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