The Natural Diterpenoid Isoforretin A Inhibits Thioredoxin-1 and Triggers Potent ROS-Mediated Antitumor Effects
Sun, Xiaoyan1,2; Wang, Weiguang3; Chen, Jiao1,2; Cai, Xueting1,2; Yang, Jie1,2; Yang, Yang1,2; Yan, Huaijiang1,2; Cheng, Xiaolan1,2; Ye, Juan1,2; Lu, Wuguang1,2; Hu, Chunping1,2; Sun, Handong3; Pu, Jianxin3; Cao, Peng1,2
2017-02-15
发表期刊CANCER RESEARCH
卷号77期号:4页码:926-936
摘要Aberrant expression of thioredoxin 1 (Trx1) plays an important role in cancer initiation and progression and has gained attention as an anticancer drug target. Here we report that the recently discovered natural diterpenoid isoforretin A (IsoA) significantly inhibits Trx1 activity and mediates anticancer effects in multiple preclinical settings. The inhibitory effect of IsoA was antagonized by free radical scavengers polyethylene glycol-catalase, polyethylene glycol superoxide dismutase, thiol- based antioxidants N-acetylcysteine and glutathione. Mass spectrometry analysis revealed that the mechanism of action was based on direct conjugation of IsoA to the Cys32/Cys35 residues of Trx1. This conjugation event attenuated reversible thiol reduction of Trx1, leading to ROS accumulation and a broader degradation of thiol redox homeostasis in cancer cells. Extending these in vitro findings, we documented that IsoA administration inhibited the growth of HepG2 tumors in a murine xenograft model of hepatocellular carcinoma. Taken together, our findings highlight IsoA as a potent bioactive inhibitor of Trx1 and a candidate anticancer natural product. (C)2016 AACR.
资助信息Priority Academic Program Development of Jiangsu Higher Education Institutions (Integration of Chinese and Western Medicine) grant; National Natural Science Foundation of China(81622048; Jiangsu Province Funds for Distinguished Young Scientists(BK20140049); Natural Science Foundation of Jiangsu Province(BK20131038); NSFC-Joint Foundation of Yunnan Province(U1302223); 81274150; 81202576; 21322204)
DOI10.1158/0008-5472.CAN-16-0987
收录类别SCI
语种英语
WOS研究方向Oncology
WOS类目Oncology
WOS记录号WOS:000393887800013
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文献类型期刊论文
条目标识符http://ir.kib.ac.cn/handle/151853/33805
专题植物化学与西部植物资源持续利用国家重点实验室
作者单位1.Nanjing Univ Chinese Med, Affiliated Hosp Integrated Tradit Chinese & Weste, Key Lab Drug Targets & Drug Leads Degenerat Dis, Nanjing, Jiangsu, Peoples R China
2.Jiangsu Prov Acad Tradit Chinese Med, Lab Cellular & Mol Biol, Nanjing, Jiangsu, Peoples R China
3.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming, Yunnan, Peoples R China
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Sun, Xiaoyan,Wang, Weiguang,Chen, Jiao,et al. The Natural Diterpenoid Isoforretin A Inhibits Thioredoxin-1 and Triggers Potent ROS-Mediated Antitumor Effects[J]. CANCER RESEARCH,2017,77(4):926-936.
APA Sun, Xiaoyan.,Wang, Weiguang.,Chen, Jiao.,Cai, Xueting.,Yang, Jie.,...&Cao, Peng.(2017).The Natural Diterpenoid Isoforretin A Inhibits Thioredoxin-1 and Triggers Potent ROS-Mediated Antitumor Effects.CANCER RESEARCH,77(4),926-936.
MLA Sun, Xiaoyan,et al."The Natural Diterpenoid Isoforretin A Inhibits Thioredoxin-1 and Triggers Potent ROS-Mediated Antitumor Effects".CANCER RESEARCH 77.4(2017):926-936.
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