ReferenceID 3459

Costunolide specifically binds and inhibits thioredoxin reductase 1 to induce apoptosis in colon cancer

Cancer Lett

Colon cancer is one of the leading causes of cancer-related deaths. A natural sesquiterpene lactone, costunolide (CTD), showed inhibition of cancer development. However, the underlying mechanisms are not known. Here, we

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Reference Id
3459
Evidence Id
20049
Core Evidence Id
20049
Source Reference Id
225
Herb2 Reference Id
HBREF000428
Subject Paper Key
HBIN021599_29037867
Pubmed Id
29037867
Doi
10.1016/j.canlet.2017.10.006
Paper Title
Costunolide specifically binds and inhibits thioredoxin reductase 1 to induce apoptosis in colon cancer
Paper Abstract
Colon cancer is one of the leading causes of cancer-related deaths. A natural sesquiterpene lactone, costunolide (CTD), showed inhibition of cancer development. However, the underlying mechanisms are not known. Here, we have examined the therapeutic activity and novel mechanisms of the anti-cancer activities of CTD in colon cancer cells. Using SPR analysis and enzyme activity assay on recombinant TrxR1 protein, our results show that CTD directly binds and inhibits the activity of TrxR1, which caused enhanced generation of ROS and led to ROS-dependent endoplasmic reticulum stress and cell apoptosis in colon cancer cells. Overexpression of TrxR1 in HCT116 cells reversed CTD-induced cell apoptosis and ROS increase. CTD treatment of mice implanted with colon cancer cells showed tumor growth inhibition and reduced TrxR1 activity and ROS level. In addition, it was observed that TrxR1 was significantly up-regulated in existing colon cancer gene database and clinically obtained colon cancer tissues. Our studies have uncovered the mechanism underlying the biological activity of CTD in colon cancer and suggest that targeting TrxR1 may prove to be beneficial as a treatment option.
Journal
Cancer Lett
Publish Year
2018
Experiment Subject
mouse
Experiment Type
Animal Experiment
Phenotype Related
Paper Title Cn
Paper Title En
Costunolide specifically binds and inhibits thioredoxin reductase 1 to induce apoptosis in colon cancer
Bilingual Status
semi_complete