کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1933111 | 1050603 | 2009 | 6 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Isoreserpine promotes β-catenin degradation via Siah-1 up-regulation in HCT116 colon cancer cells Isoreserpine promotes β-catenin degradation via Siah-1 up-regulation in HCT116 colon cancer cells](/preview/png/1933111.png)
Aberrant accumulation of intracellular β-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 β-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 β-catenin by up-regulation of Siah-1 in HEK293 and HCT116 colon cancer cells. Moreover, isoreserpine repressed the expression of β-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.
Journal: Biochemical and Biophysical Research Communications - Volume 387, Issue 3, 25 September 2009, Pages 444–449