Negative regulation of beta-catenin/Tcf signaling by naringenin in AGS gastric cancer cell |
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Authors: | Lee Ju Hyung Park Chi Hoon Jung Kyung Chae Rhee Ho Sung Yang Chul Hak |
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Institution: | Division of Chemistry and Molecular Engineering, Seoul National University, Seoul 151-742, Republic of Korea. |
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Abstract: | Functional activation of beta-catenin/Tcf signaling plays an important role in early events in carcinogenesis. We examined the effect of naringenin against beta-catenin/Tcf signaling in gastric cancer cells. Reporter gene assay showed that naringenin inhibited beta-catenin/Tcf signaling efficiently. In addition, the inhibition of beta-catenin/Tcf signaling by naringenin in HEK293 cells transiently transfected with constitutively mutant beta-catenin gene, whose product is not phosphorylated by GSK3beta, indicates that its inhibitory mechanism was related to beta-catenin itself or downstream components. To investigate the precise inhibitory mechanism, we performed immunofluorescence, Western blot, and EMSA. As a result, our data revealed that the beta-catenin distribution and the levels of nuclear beta-catenin and Tcf-4 proteins were unchanged after naringenin treatment. Moreover, the binding activities of Tcf complexes to consensus DNA were not affected by naringenin. Taken together, these data suggest that naringenin inhibits beta-catenin/Tcf signaling in gastric cancer with unknown mechanisms. |
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Keywords: | β-Catenin/Tcf signaling Naringenin Nuclear β-catenin Mechanism |
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