Isoreserpine promotes beta-catenin degradation via Siah-1 up-regulation in HCT116 colon cancer cells.

Article Details

Citation

Copy to clipboard

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Reserpine	Approved Investigational Withdrawn	CCND1	595	downregulated	Reserpine results in decreased expression of CCND1 mRNA	11q13.3
Reserpine	Approved Investigational Withdrawn	SIAH1	6477	upregulated	Reserpine results in increased expression of SIAH1 mRNA	16q12.1