Journal
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
Volume 59, Issue 17, Pages 9683-9690Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jf2021489
Keywords
osthole; epithelial-mesenchymal transition; c-Met; Akt; mTOR
Funding
- National Science Council of the Republic of China [NSC 96-2323-B-039-001, NSC 97-2323-B-039-001]
- Department of Health (Taiwan), China Medical University Hospital Cancer Research Center of Excellence [DOH100-TD-C-111-005]
- China Medical University [CMU99-S-34, CMU99-TC-02]
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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.
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