Isoreserpine promotes beta-catenin degradation via Siah-1 up-regulation in HCT116 colon cancer cells.
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Gwak J, Song T, Song JY, Yun YS, Choi IW, Jeong Y, Shin JG, Oh S
Isoreserpine promotes beta-catenin degradation via Siah-1 up-regulation in HCT116 colon cancer cells.
Biochem Biophys Res Commun. 2009 Sep 25;387(3):444-9. doi: 10.1016/j.bbrc.2009.07.027. Epub 2009 Jul 14.
- PubMed ID
- 19607803 [ View in PubMed]
- Abstract
Aberrant accumulation of intracellular beta-catenin in intestinal epithelial cells is a frequent early event during the development of colon cancer. To identify small molecules that decrease the level of intracellular beta-catenin, we performed cell-based chemical screening using genetically engineered HEK293 reporter cells to detect compounds that inhibit TOPFlash reporter activity, which was stimulated by Wnt3a-conditioned medium. We found that isoreserpine promoted the degradation of intracellular beta-catenin by up-regulation of Siah-1 in HEK293 and HCT116 colon cancer cells. Moreover, isoreserpine repressed the expression of beta-catenin/T-cell factor (TCF)-dependent genes, such as cyclin D1 and c-myc, resulting in the suppression of HCT116 cell proliferation. Our findings suggest that isoreserpine can potentially be used as a chemotherapeutic agent against colon cancer.
DrugBank Data that Cites this Article
- Pharmaco-transcriptomics
Drug Drug Groups Gene Gene ID Change Interaction Chromosome Reserpine Approved Investigational Withdrawn CCND1 595 downregulated Reserpine results in decreased expression of CCND1 mRNA 11q13.3 Reserpine Approved Investigational Withdrawn SIAH1 6477 upregulated Reserpine results in increased expression of SIAH1 mRNA 16q12.1