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標題: Osthole Suppresses Hepatocyte Growth Factor (HGF)-Induced Epithelial-Mesenchymal Transition via Repression of the c-Met/Akt/mTOR Pathway in Human Breast Cancer Cells
作者: Hung, C.M.
Kuo, D.H.
Chou, C.H.
Su, Y.C.
Ho, C.T.
Way, T.D.
關鍵字: osthole;epithelial-mesenchymal transition;c-Met;Akt;mTOR;fatty-acid synthase;cnidium-monnieri;met receptor;stem-cells;metastasis;expression;mice;activation;luteolin
Project: Journal of Agricultural and Food Chemistry
期刊/報告no:: Journal of Agricultural and Food Chemistry, Volume 59, Issue 17, Page(s) 9683-9690.
Substantial activation of the HGF/c-Met signaling pathway is involved in the progression of several types of cancers and associated with increased tumor invasion and metastatic potential. Underlying HGF-induced tumorigenesis, epithelial to mesenchymal transition (EMT) shows a positive correlation with progression in patients. We previously determined that osthole is a potent fatty acid synthase (FASN) inhibitor. FASN is implicated in Cancer progression and may regulate lipid raft function. We therefore examined whether osthole could block HGF-induced tumorigenesis by disrupting lipid rafts. Here, we found that osthole could abrogate HGF-induced cell scattering, migration, and invasion in MCF-7 breast cancer cells. Osthole also effectively inhibited the HGF-induced decrease of E-cadherin and increase of vimentin via down-regulation of phosphorylated Akt and mTOR. Interestingly, osthole blocked HGF-induced c,,Met:phosphorylation and repressed the expression of total c-Met protein in MCF-7 cells. In addition, C75, a pharmacological inhibitor of FASN, repressed the expression of total c-Met protein in MCF-7 cells. Consistent with a role for FASN, loss of c-Met in cells treated with osthole was prevented by the exogenous addition of palmitate. Briefly, our result suggests a connection between FASN activity and c-Met, protein expression and that osthole is a potential compound for breast cancer therapy by targeting the major pathway of HGF/C-Met-induced EMT.
ISSN: 0021-8561
DOI: 10.1021/jf2021489
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