title: Ursolic acid inhibits epithelial-mesenchymal transition by suppressing the expression of astrocyte-elevated gene-1 in human nonsmall cell lung cancer A549 cells.
abstract: Lung cancer is one of the most death-related cancers worldwide. Ursolic acid (UA), a pentacyclic triterpene acid, has a wide range of anticancer functions such as proapoptosis, antiangiogenesis, and antimetastasis. This study was carried out to explore the inhibition mechanism of UA on metastasis of lung cancer A549 cells. First, we found that UA inhibited the metastasis of lung cancer cells in a concentration-dependent manner through an adhesion assay, a cell wound healing assay, and a transwell migration assay in vitro. In addition, after treatment with UA, the A549 cells showed decreased expression of astrocyte-elevated gene-1 (AEG-1) accompanied by upregulation of E-cadherin and downregulation of N-cadherin and vimentin, which have been reported to characterize the epithelial-mesenchymal transition (EMT). Further results also confirmed that the expression of vimentin was decreased by the siRNA technique to directly knock down AEG-1 expression, indicating that AEG-1 was involved in UA-mediated EMT inhibition. Furthermore, our results showed that UA suppressed the expression level of AEG-1 by repressing nuclear factor-κB signaling. Altogether, UA inhibited the EMT by suppressing the expression of AEG-1, correlating with inhibition of nuclear factor-κB in A549 cells. These findings suggested that UA was a potent anti-lung cancer agent, and it may be able to prevent invasion and metastasis of lung cancer cells.
authors.affiliation: State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu 210009 People's Republic of China.
authors.forename: Kunmei
authors.initials: K
authors.lastname: Liu
authors.forename: Le
authors.initials: L
authors.lastname: Guo
authors.forename: Lin
authors.initials: L
authors.lastname: Miao
authors.forename: Weiwei
authors.initials: W
authors.lastname: Bao
authors.forename: Jue
authors.initials: J
authors.lastname: Yang
authors.forename: Xiaokang
authors.initials: X
authors.lastname: Li
authors.forename: Tao
authors.initials: T
authors.lastname: Xi
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D015820:Cadherins / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008565:Membrane Proteins; D016328:NF-kappa B / Q000378:metabolism; D016601:RNA-Binding Proteins; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014315:Triterpenes / Q000494:pharmacology*; D014746:Vimentin / Q000235:genetics; D000097245:Ursolic Acid
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D015820:Cadherins; D015815:Cell Adhesion Molecules; D008565:Membrane Proteins; D016328:NF-kappa B; D016601:RNA-Binding Proteins; D014315:Triterpenes; D014746:Vimentin; D000097245:Ursolic Acid; C483039:MTDH protein, human