ReferenceID 3475

Promotion of HeLa cells apoptosis by cynaropicrin involving inhibition of thioredoxin reductase and induction of oxidative stress

Free Radic Biol Med

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 thioredoxi

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Reference Id
3475
Evidence Id
20065
Core Evidence Id
20065
Source Reference Id
254
Herb2 Reference Id
HBREF000491
Subject Paper Key
HBIN022473_30880248
Pubmed Id
30880248
Doi
10.1016/j.freeradbiomed.2019.03.014
Paper Title
Promotion of HeLa cells apoptosis by cynaropicrin involving inhibition of thioredoxin reductase and induction of oxidative stress
Paper Abstract
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 selenocysteine-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.
Journal
Free Radic Biol Med
Publish Year
2019
Experiment Subject
hela cells
Experiment Type
Cell Experiment
Phenotype Related
Paper Title Cn
Paper Title En
Promotion of HeLa cells apoptosis by cynaropicrin involving inhibition of thioredoxin reductase and induction of oxidative stress
Bilingual Status
semi_complete