p38 MAPK Signaling Mediates Mitochondrial Apoptosis in Cancer Cells Induced by Oleanolic Acid

	p38 MAPK Signaling Mediates Mitochondrial Apoptosis in Cancer Cells Induced by Oleanolic Acid
	Liu, Jia 1; Wu, Ning 1; Ma, Lei-Na 3; Zhong, Jia-Teng 6; Liu, Ge 1,4; Zheng, Lan-Hong 2; Lin, Xiu-Kun 1,5
刊名	ASIAN PACIFIC JOURNAL OF CANCER PREVENTION
	2014
卷号	15 期号:11 页码:4519-4525
关键词	Oleanolic acid apoptosis p38 MAPK cancer ROS
通讯作者	Zheng, LH (reprint author), Chinese Acad Fishery Sci, Yellow Sea Fisheries Res Inst, Qingdao, Peoples R China.
英文摘要	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.
学科主题	Oncology
收录类别	SCI
语种	英语
WOS记录号	WOS:000338634900023
内容类型	期刊论文
源URL	[http://ir.qdio.ac.cn/handle/337002/24235]
专题	海洋研究所_海洋生物技术研发中心
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
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.,...&Lin, Xiu-Kun.(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.