The Flavonols Quercetin, Kaempferol, and Myricetin Inhibit Hepatocyte Growth Factor-Induced Medulloblastoma Cell Migration
| Autor: | Mathieu Provençal, Denis Gingras, Sylvie Lamy, David P. Labbé, Richard Béliveau, Dominique Boivin |
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| Rok vydání: | 2009 |
| Předmět: |
medicine.medical_specialty
Indoles Medicine (miscellaneous) Biology Gene Expression Regulation Enzymologic Piperazines Receptor tyrosine kinase chemistry.chemical_compound Cell Movement Cell Line Tumor Proto-Oncogene Proteins Internal medicine medicine Humans Receptors Growth Factor Kaempferols Phosphorylation Cell Shape Protein Kinase Inhibitors Protein kinase B Flavonoids Medulloblastoma Sulfonamides Nutrition and Dietetics Hepatocyte Growth Factor Proto-Oncogene Proteins c-met medicine.disease Endocrinology chemistry Cancer research biology.protein Quercetin Hepatocyte growth factor Myricetin Kaempferol Proto-Oncogene Proteins c-akt Tyrosine kinase medicine.drug |
| Zdroj: | The Journal of Nutrition. 139:646-652 |
| ISSN: | 0022-3166 |
| Popis: | Medulloblastoma, the most common malignant brain tumor in children, is a highly metastatic disease, with up to 30% of children having evidence of disseminated disease at presentation. Recently, the hepatocyte growth factor (HGF) and its receptor, the tyrosine kinase Met, have emerged as key components of human medulloblastoma growth and metastasis, suggesting that inhibition of this pathway may represent an attractive target for the prevention and treatment of this disease. Using immunoblotting procedures, we observed that the dietary-derived flavonols quercetin, kaempferol, and myricetin inhibited HGF/Met signaling in a medulloblastoma cell line (DAOY), preventing the formation of actin-rich membrane ruffles and resulting in the inhibition of Met-induced cell migration in Boyden chambers. Furthermore, quercetin and kaempferol also strongly diminished HGF-mediated Akt activation. Interestingly, the inhibitory effects of quercetin on the tyrosine kinase receptor Met [half-maximal inhibitory effect (IC(50)) of 12 micromol/L] or on the Met-induced activation of Akt (IC(50) of 2.5 micromol/L) occurred at concentrations achievable through dietary approaches. These results highlight quercetin, kaempferol, and myricetin as dietary-derived inhibitors of Met activity and suggest that this inhibitory effect may contribute to the chemopreventive properties of these molecules. |
| Databáze: | OpenAIRE |
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