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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Record Fields
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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