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Alantolactone Inhibits Cell Proliferation by Interrupting the Interaction between Cripto-1 and Activin Receptor Type II A in Activin Signaling Pathway
- Source :
- SLAS Discovery: Advancing Life Sciences R&D; June 2011, Vol. 16 Issue: 5 p525-535, 11p
- Publication Year :
- 2011
-
Abstract
- It has been suggested that deregulation of activin signaling contributes to tumor formation. Activin signaling is blocked in cancer cells due to the complex formed by Cripto-1, activin, and activin receptor type II (ActRII). In this study, the authors used a mammalian two-hybrid system to construct a drug screening model to obtain a small molecular inhibitor capable of interrupting the interaction between Cripto-1 and ActRII. They screened 300 natural components and identified alantolactone. Data suggested that alantolactone induced activin/SMAD3 signaling in human colon adenocarcinoma HCT-8 cells. The authors also found that alantolactone exhibited antiproliferative function specific to tumor cells, with almost no toxicity to normal cells at a concentration of 5 µg/mL. Furthermore, they proved that the antiproliferative function of alantolactone was activin/SMAD3 dependent. These results suggest that alantolactone performs its antitumor effect by interrupting the interaction between Cripto-1 and the activin receptor type IIA in the activin signaling pathway. Moreover, screening for inhibitors of Cripto-1/ActRII is a potentially beneficial approach to aid in discovering novel cancer treatment.
Details
- Language :
- English
- ISSN :
- 24725552 and 24725560
- Volume :
- 16
- Issue :
- 5
- Database :
- Supplemental Index
- Journal :
- SLAS Discovery: Advancing Life Sciences R&D
- Publication Type :
- Periodical
- Accession number :
- ejs59462885
- Full Text :
- https://doi.org/10.1177/1087057111398486