title: Licochalcone A inhibits the migration and invasion of human lung cancer cells via inactivation of the Akt signaling pathway with downregulation of MMP-1/-3 expression.
abstract: Licochalcone A (LicA), a major phenolic constituent of Glycyrrhiza inflata, has been reported to exhibit anti-tumor, anti-inflammatory, and anti-metastatic properties in various cancer cells and animal models. The aim of this study was to determine the anti-tumor effects of LicA on lung cancer cells. The results indicated that LicA exhibited effective inhibition of cell migration and invasion of A549 and H460 cells under non-cytotoxic concentrations. Furthermore, LicA was also found to significantly inhibit the proteins and messenger RNA (mRNA) expression of MMP-1 and MMP-3 in A549 cells. Moreover, treatment of A549 cells with LicA-inhibited activation of the phosphorylation of Akt and inhibition of Akt by LY294002 (PI3K inhibitor) or transfection with the constitutive active-Akt (CA-Akt) expression vector significantly abolished the LicA-inhibited migration and invasion through activation of the Akt pathway. Further mechanistic studies revealed that LicA inhibits Akt signaling pathways and downstream transcription factors Sp1 expression. These findings imply a critical role for Akt inhibition in the LicA-inhibited migration and invasion of lung cancer cells. Thus, LicA might be used as an anti-invasive agent in the treatment of lung cancer.
authors.affiliation: Visiting staff, Division of General thoracic Surgery, Department of surgery, Changhua Christian Hospital, Changhua, Taiwan.
authors.forename: Hung-Che
authors.initials: HC
authors.lastname: Huang
authors.forename: Lo-Lin
authors.initials: LL
authors.lastname: Tsai
authors.forename: Jen-Pi
authors.initials: JP
authors.lastname: Tsai
authors.forename: Shu-Ching
authors.initials: SC
authors.lastname: Hsieh
authors.forename: Shun-Fa
authors.initials: SF
authors.lastname: Yang
authors.forename: Jung-Tsung
authors.initials: JT
authors.lastname: Hsueh
authors.forename: Yi-Hsien
authors.initials: YH
authors.lastname: Hsieh
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D047188:Chalcones / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism*; D020781:Matrix Metalloproteinase 1 / Q000235:genetics* / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D047188:Chalcones; D016329:Sp1 Transcription Factor; D051057:Proto-Oncogene Proteins c-akt; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1; C070840:licochalcone A