Negative regulation of beta-catenin/Tcf signaling by naringenin in AGS gastric cancer cell.
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.
Lee
Ju Hyung
JH
Division of Chemistry and Molecular Engineering, Seoul National University, Seoul 151-742, Republic of Korea.
Park
Chi Hoon
CH
Jung
Kyung Chae
KC
Rhee
Ho Sung
HS
Yang
Chul Hak
CH
D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001483:Base Sequence; D015153:Blotting, Western; D045744:Cell Line, Tumor; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D044950:Flavanones / Q000494:pharmacology*; D006801:Humans; D051821:Lymphoid Enhancer-Binding Factor 1; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects*; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D051176:beta Catenin
D000897:Anti-Ulcer Agents; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D044950:Flavanones; D051821:Lymphoid Enhancer-Binding Factor 1; D015534:Trans-Activators; D014157:Transcription Factors; D051176:beta Catenin; C005273:naringenin