期刊
JOURNAL OF CANCER
卷 11, 期 13, 页码 3725-3735出版社
IVYSPRING INT PUBL
DOI: 10.7150/jca.40983
关键词
Brevilin A; NSCLC; ROS; STAT3; SPR; apoptosis
类别
资金
- National Natural Science Foundation of China [81672944, 81650110526]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (Integration of Chinese and Western Medicine)
Sesquiterpene lactones have been shown to be promising leads for anticancer drug development. Brevilin A (BLN-A), a sesquiterpene lactone compound of Centipeda minima has been shown to exhibit anticancer effects against various cancer cells. However, the anticancer mechanism and cellular targets of BLN-A remain elusive. Here in this study, BLN-A inhibits proliferation and induces cell morphological changes in A549 and NCI-H1650 non-small cell lung cancer cells in a dose-dependent manner. Moreover, BLN-A increased ROS generation and bax/bcl-2 ratio while decreased intracellular glutathione (GSH), and mitochondrial membrane potential which resulted in induction of apoptosis as evident by annexin-V/FITC staining, caspase-3 activation and PARP cleavage. Supplementation of cells with NAC (ROS Scavenger) effectively protected the cells from BLN-A-induced apoptosis. Finally, BLN-A inhibited constitutive as well as IL-6- and EGF-induced STAT3 activation at Tyr705. Using molecular docking and SPR analyses, we found that BLN-A directly binds with STAT3 and thereby inhibits its activation. Knocking down of STAT3 by stable transfection with shRNA suppressed growth and augmented cytotoxicity of BLN-A, indicating the key role of STAT3 in BLN-A-mediated apoptosis. Cumulative findings suggest that BLN-A is a promising lead structure for developing it into a potent STAT3 inhibitor and therapeutic agent against NSCLC as well.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据