کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10770993 | 1050837 | 2005 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Quercetin, a potent inhibitor against β-catenin/Tcf signaling in SW480 colon cancer cells
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
Dysregulation of Wnt/β-catenin pathway plays a central role in early events in colorectal carcinogenesis. We examined the effect of quercetin, a famous anti-tumor agent, against β-catenin/Tcf signaling in SW480 cells. Quercetin inhibited the transcriptional activity of β-catenin/Tcf in SW480 and also in HEK293 cells transiently transfected with constitutively active mutant β-catenin gene, whose product is not induced to be degraded by APC-Axin-GSK3β complex, so we concluded that its inhibitory mechanism was related to β-catenin itself or downstream components. To investigate the precise inhibitory mechanism, we performed EMSA showing that binding of the Tcf complexes to its specific DNA-binding sites was strongly suppressed by quercetin. Immunoprecipitation analysis also showed that the binding of β-catenin to Tcf-4 was also disrupted by quercetin. Western blot analysis proved these decreased bindings resulted from decreased level of β-catenin and Tcf-4 product in nucleus caused by quercetin. Together, we suggest that quercetin is an excellent inhibitor of β-catenin/Tcf signaling in SW480 cell lines, and the reduced β-catenin/Tcf transcriptional activity is due to the decreased nuclear β-catenin and Tcf-4 proteins.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 328, Issue 1, 4 March 2005, Pages 227-234
Journal: Biochemical and Biophysical Research Communications - Volume 328, Issue 1, 4 March 2005, Pages 227-234
نویسندگان
Chi Hoon Park, Joon Young Chang, Eun Ryeong Hahm, Seyeon Park, Hyun-Kyung Kim, Chul Hak Yang,