α- and γ-Mangostin Inhibit Wnt Signaling through Transcriptional Regulation of β-catenin
- α- and γ-Mangostin Inhibit Wnt Signaling through Transcriptional Regulation of β-catenin
- 유지혜; 진용원; 김진웅; 강경수; 이샛별; 노주원
- Mangostins; Wnt signaling; Transcriptional regulation; Colon cancer
- Issue Date
- 한국생화학분자생물학회 동계학술대회
- Aberrant activation of Wnt signaling via genetic errors of β-catenin or APC has a crucial role in colon carcinogenesis. To date the agents controlling Wnt signaling have reported in many studies, but there is no known compound to control the expression of β-catenin gene specifically. Here, we studied two xanthones, α- and γ-mangostin, regulated transcriptional levels of β-catenin. α- and γ-Mangostin inhibited colon cancer cell proliferation as well as TCF/β-catenin transcriptional activity in two colon cancer cell lines, HCT116 and SW480 have different genetic errors. Although the degradation of β-catenin is known to be rare in HCT116 cells due to the critical mutation of β-catenin, the effect of mangostins showed stronger in HCT116 than SW480 cells. Also, the significant degradation of β-catenin was observed in both cells, but the phosphorylation of β-catenin for the degradation was not changed at all while the mRNA levels of β–catenin markedly decreased. Furthermore, the treatment of MG-132, a proteosome inhibitor, and LiCl, GSK-3β inhibitor, has no influence on the effect of mangostins for inhibiting TCF/β-catenin transcriptional activity and the protein levels of β-catenin. In conclusion, α- and γ-mangostin inhibit Wnt signaling due to transcriptional regulation of β-catenin.
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