کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5842405 1124750 2013 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
3-Methoxyapigenin modulates β-catenin stability and inhibits Wnt/β-catenin signaling in Jurkat leukemic cells
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
3-Methoxyapigenin modulates β-catenin stability and inhibits Wnt/β-catenin signaling in Jurkat leukemic cells
چکیده انگلیسی

AimsAberrant activation of Wnt/β-catenin signaling has been implicated in carcinogenesis. Identification of inhibitors of this pathway may help in cancer therapy. The purpose of this study is to investigate the inhibitory effect of 3-methoxyapigenin (3-MA) with β-catenin/LEF reporter system. The anti-cancer mechanisms in Jurkat leukemic cells were also examined.Main methodsHEK 293-TOP/FOP reporter cells were used to determine the inhibitory effect of 3-MA on Wnt/β-catenin pathway. We also used Jurkat-TOP reporter cells to confirm the inhibitory effect and the action mechanisms of 3-MA. Target genes and cell proliferation were analyzed by RT-PCR and 3H-thymidine uptake assay. The effects of 3-MA on β-catenin phosphorylation was determined by Western blotting and by in vitro kinase assays. β-catenin translocation and its transactivation were verified by cellular fractionation and EMSA.Key findings3-MA inhibited Wnt-3A-induced luciferase activity in the HEK 293-TOP/FOP reporter system. Western blotting analysis showed that phosphorylation sites in β-catenin by glycogen synthase kinase-3β (GSK-3β) and casein kinase 2 (CK2) were inhibited by 3-MA in Jurkat. In parallel, in vitro kinase assays verified this effect. As a result, total β-catenin turnover remained balanced by this dual inhibitory effect of 3-MA. Although the β-catenin protein level remained unchanged, 3-MA did inhibit β-catenin translocation. Finally, we found that the β-catenin/LEF transcriptional activity, expression of c-myc and cyclin-D3, and cell proliferation were inhibited by 3-MA.Significance3-MA modulates the turnover of β-catenin and suppresses the Wnt/β-catenin signaling pathway through inhibition of β-catenin translocation. We suggested that 3-MA has potential as an anti-cancer drug.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Life Sciences - Volume 92, Issue 12, 9 April 2013, Pages 677-686
نویسندگان
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