Dehydrocostus lactone, a natural sesquiterpene lactone, suppresses the biological characteristics of glioma, through inhibition of the NF-κB/COX-2 signaling pathway by targeting IKKβ.
机构：[1]The First Affliated Hospital & Key Laboratory of Pharmacokinetic and Drug Transport of Liaoning, College of Pharmacy, Academy of Integrative Medicine, Dalian Medical University, Dalian, 116044, China大连医科大学附属第一医院[2]Key Laboratory of Digital Quality Evaluation of Chinese Material Medical of State Administration of TCM, Guangdong Pharmaceutical University, Guangdong, China.
Dehydrocostus lactone (DHE), a natural sesquiterpene lactone, has been used for treatment of various diseases with its anti-inflammatory activity. Recently, it has caused extensive interest in researchers due to it has anti-cancer abilities in some types of carcinomas. However, the anti-cancer effect and mechanism of DHE in glioma remains unclear. The present study conducted to determine the biological effects of DHE on the glioblastoma cells, as well as the mechanisms underlying these effects. After treatment with DHE, the glioblastoma (U118, U251 or U87) cells were significantly inhibited in their viability, proliferation and migration. At the meantime, DHE also induced mitochondria-mediated apoptosis by promoting the release of cytochrome c into cytosol, which activating caspase signaling pathway. Furthermore, our results fully demonstrate that DHE significantly suppressed COX-2 expression by inhibiting the phosphorylation of IKKβ via targeting the ATP-binding site, thereby abrogating NF-κB binding and p300 recruitment to COX-2 promoter. Moreover, the current study firstly demonstrated that DHE can cross blood-brain barrier (BBB). In addition, treatment with DHE markedly inhibited neoplastic weight and volume without the notable adverse effects in the xenograft nude mice model, and these effects may be mediated through inhibition of the IKKβ/NF-κB/COX-2 signaling pathway. These findings provide the pharmacological evidence for development of DHE as a potential agent against glioma.
基金：
We thank the NSFC (81622047, 81473334
and 81172180), Dalian Outstanding Youth Science
and Technology Talent (2015J12JH201),
Distinguished professor of Liaoning Province,
Project sponsored by Liaoning BaiQianWan
Talents Program and Innovation Team of Dalian
Medical University for financial support.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2016]版：
大类|2 区医学
小类|3 区肿瘤学
最新[2025]版：
大类|3 区医学
小类|4 区肿瘤学
第一作者：
第一作者机构：[1]The First Affliated Hospital & Key Laboratory of Pharmacokinetic and Drug Transport of Liaoning, College of Pharmacy, Academy of Integrative Medicine, Dalian Medical University, Dalian, 116044, China
共同第一作者：
通讯作者：
通讯机构：[1]The First Affliated Hospital & Key Laboratory of Pharmacokinetic and Drug Transport of Liaoning, College of Pharmacy, Academy of Integrative Medicine, Dalian Medical University, Dalian, 116044, China[2]Key Laboratory of Digital Quality Evaluation of Chinese Material Medical of State Administration of TCM, Guangdong Pharmaceutical University, Guangdong, China.[*1]The First Affliated Hospital & Key Laboratory of Pharmacokinetic and Drug Transport of Liaoning, College of Pharmacy, Academy of Integrative Medicine, Dalian Medical University, No. 9 West Section, Lvshun South Road, Lvshunkou District, Dalian 116044, China.
推荐引用方式(GB/T 7714)：
Wang Jinkui,Yu Zhenlong,Wang Chao,et al.Dehydrocostus lactone, a natural sesquiterpene lactone, suppresses the biological characteristics of glioma, through inhibition of the NF-κB/COX-2 signaling pathway by targeting IKKβ.[J].American journal of cancer research.2017,7(6):1270-1284.
APA：
Wang Jinkui,Yu Zhenlong,Wang Chao,Tian Xiangge,Huo Xiaokui...&Xu Yinghui.(2017).Dehydrocostus lactone, a natural sesquiterpene lactone, suppresses the biological characteristics of glioma, through inhibition of the NF-κB/COX-2 signaling pathway by targeting IKKβ..American journal of cancer research,7,(6)
MLA：
Wang Jinkui,et al."Dehydrocostus lactone, a natural sesquiterpene lactone, suppresses the biological characteristics of glioma, through inhibition of the NF-κB/COX-2 signaling pathway by targeting IKKβ.".American journal of cancer research 7..6(2017):1270-1284
