期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 135, 期 -, 页码 216-226出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2019.03.014
关键词
Thioredoxin reductase; Cynaropicrin; Reactive oxygen species (ROS); Redox regulation; Oxidative stress; Apoptosis
资金
- National Natural Science Foundation of China [21572093, 21778028]
- Natural Science Foundation of Gansu Province [18JR3RA296]
- Lanzhou University (the Fundamental Research Funds for the Central Universities) [lzujbky-2018-39]
- 111 Project
Cancer is considered as one of the highly mortal diseases globally. This is largely due to the lack of efficacious medicines for tumors, and thus development of potent anticancer agents is urgently needed. The thioredoxin (Trx) system is crucial to the survival ability of cells and its expression is up-regulated in many human tumors. Recently, increasing evidence has been established that mammalian thioredoxin reductase (TrxR), a seleno-cysteine-containing protein and the core component of the thioredoxin system, is a promising therapeutic target. The sesquiterpene lactone compound cynaropicrin (CYN), a major component of Cynara scolymus L., has shown multiple pharmacological functions, especially the anticancer effect, in many experimental models. Most of these functions are concomitant with the production of reactive oxygen species (ROS). Nevertheless, the target of this promising natural anticancer product in redox control has rarely been explored. In this study, we showed that CYN induces apoptosis of Hela cells. Mechanistic studies demonstrated that CYN impinges on the thioredoxin system via inhibition of TrxR, which leads to Trx oxidation and ROS accumulation in HeLa cells. Particularly, the cytotoxicity of CYN is enhanced through the genetic knockdown of TrxR, supporting the pharmacological effect of CYN is relevant to its inhibition of TrxR. Together, our studies reveal an unprecedented mechanism accounting for the anticancer effect of CYN and identify a promising therapeutic agent worthy of further development for cancer therapy.
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