p38 MAPK Signaling Mediates Mitochondrial Apoptosis in Cancer Cells Induced by Oleanolic Acid
文献类型: 外文期刊
作者: Liu, Jia 1 ; Wu, Ning 1 ; Ma, Lei-Na 3 ; Zhong, Jia-Teng 6 ; Liu, Ge 1 ; Zheng, Lan-Hong 2 ; Lin, Xiu-Kun 1 ;
作者机构: 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
关键词: Oleanolic acid;apoptosis;p38 MAPK;cancer;ROS
期刊名称:ASIAN PACIFIC JOURNAL OF CANCER PREVENTION ( 影响因子:2.514; 五年影响因子:2.267 )
ISSN: 1513-7368
年卷期: 2014 年 15 卷 11 期
页码:
收录情况: SCI
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.
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